JAMDA 15 (2014) 234e239
JAMDA journal homepage: www.jamda.com
Review
Management of Neurogenic Orthostatic Hypotension Debbie Arbique DNP, FNP-C, RN, CEN, CFN a, Dennis Cheek PhD, RN b, Mark Welliver DNP, CRNA, ARNP b, Wanpen Vongpatanasin MD, FAHA, FACC a, * a b
UT Southwestern Medical Center at Dallas, Internal Medicine, Cardiology Division: Hypertension Section, Dallas, TX Harris College of Nursing and Health Sciences and School of Nurse Anesthesia, Texas Christian University, Fort Worth, TX
a b s t r a c t Keywords: Neurogenic orthostatic hypotension physiology and pathophysiology with standing supine hypertension neurogenic diagnostic tests pharmacological and nonpharmacological mortality morbidity
The burden of orthostatic hypotension (OH) on public health is a universally recognized enigmatic clinical condition that is associated with significant increases on morbidity and mortality rates, and can take a major toll on one’s quality of life. Orthostatic hypotension is predictive of vascular deaths from acute myocardial infarction, strokes in the middle aged population, and increases mortality rates when associated with diabetes, hypertension, Parkinson’s disease, and patients receiving renal dialysis. The consensus definition for OH is a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 minutes of quiet standing. Because neurogenic OH is often accompanied by supine hypertension, the treatment program should aim toward minimizing OH and the potential fall injuries related to cerebral hypoperfusion without exacerbating nocturnal hypertension that may lead to excessive cardiovascular complications. Ó 2014 - American Medical Directors Association, Inc. All rights reserved.
Orthostatic hypotension (OH) in the aging population is a major burden on the public healthcare system. While the incidence of OH is low in the general population (about 0.5% incidence), there is a 30% incidence in the aging population starting after 60 years of age and up to 64% incidence in nursing home settings.1,2 OH is a dynamic state that is not a disease or a pathologic entity in itself, but rather it is a physical sign.3 The consensus definition for OH is a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 minutes of quiet standing.4 6 OH is predictive of vascular deaths from acute myocardial infarction and strokes in the middle aged population.5,7 Neurogenic OH is a more complex form of OH involving the central nervous system. Neurogenic OH is well associated with increased mortality rates for diabetes, hypertension, Parkinson’s disease, and patients receiving renal dialysis.5,8,9 Many studies divide neurogenic OH into 2 subcategories; a patient can be symptomatic or asymptomatic during OH episodes.1,4,10 Symptomatic OH usually occurs during postural changes, prolonged motionless standing, stressful events, dehydration, time of day, alcohol ingestion, carbohydrateheavy meals, heat exposure or fever, or valsalva maneuvers from straining. Symptoms include dizziness, lightheadedness, faintness,
The authors declare no conflicts of interest. * Address correspondence to Wanpen Vongpatanasin, MD, FAHA, FACC, UT Southwestern Medical Center at Dallas, Internal Medicine, Cardiology Division: Hypertension Section, 5323 Harry Hines Blvd, Dallas, TX 75390-8586. E-mail address: [email protected] (W. Vongpatanasin).
syncope episodes, inability to stand or walk, neck pain, chest pain, and cognitive impairment. Dizziness and syncope events account for up to 21% of patients presenting to the emergency department.3 In the United States, syncope related events are the sixth most common cause for hospitalizations for individuals 65 years of age or older.11 While asymptomatic patients do not show symptoms, they are at high risk for neurologic or cardiovascular events.12 Patients with supine hypertension can also exhibit OH, and the prevalence of OH in elderly hypertensive patients is 10%e30%.4,13 While there are many research publications and book chapters written on best evidence-based approaches to care for neurogenic OH patients, this valuable information has not been formally translated or disseminated into clinical practice.
Review of Literature The burden of OH on public health is a universally recognized enigmatic clinical condition that is associated with significant increases in morbidity and mortality rates, that can take a major toll on one’s quality of life1,8,14 17 A comprehensive literature review searched for evidence-based clinical practice on the topic of neurogenic OH by using Medline databases of Academic Search Premier, PubMed, OVID, Cochrane, and CINAHL. The key search words “orthostatic hypotension” were used in conjunction with the following terms and phrases for the literature search: “physiology of standing,” “pathophysiology with
1525-8610/$ - see front matter Ó 2014 - American Medical Directors Association, Inc. All rights reserved. http://dx.doi.org/10.1016/j.jamda.2013.10.014
D. Arbique et al. / JAMDA 15 (2014) 234e239
standing,” “pathophysiology of neurogenic orthostatic hypotension and supine hypertension,” “neurogenic (orthostatic hypotension) diagnosis,” “diagnostic tests,” “pharmacological management,” “nonpharmacological management,” and mortality and morbidity. All literature published within the past 35 years was considered for review. Articles that specifically addressed the key terms in their title had their abstract reviewed. Over 300 abstracts were reviewed, and 67 articles were retrieved in full based on usefulness to develop clinical guidelines for the management of orthostatic hypotension.
Epidemiology A multicenter observational, longitudinal study conducted by Rutan of 5201 men and women aged 65 years or older showed the prevalence of symptomatic OH to be 14.8% higher compared with younger age groups with a noted increase to 26% in those 85 years and older.18 This finding was statistically significant demonstrating a strong association between OH and aging. In 2008, persons 65 years or older was 38.9 million, which represents 12.8% of the US population (1 in every 8 Americans) and by 2030, the aging population is expected to grow to by 20%, to reach 71.5 million.19 In another longitudinal study conducted by Eigenbrodt et al from 1987e1996, 11,707 persons were followed who were stroke free and without overt heart disease at baseline over an 8-year period.20 The study identified a higher incidence of stroke in patients with OH compared with those without OH. The study also revealed an increased incidence for having a stroke being linked to the degrees of severity of systolic or diastolic OH, and there was a strong association with hypertension, diabetes, or Parkinson’s disease. In a prospective study, Ko et al21 supported these findings for patients having diabetes and neurogenic autonomic OH, were at a much higher risk for future ischemic stroke events. Vinik et al 7 conducted a meta-analysis of 42 published studies from 1960 to 1998 that showed diabetic patients with autonomic failure were at the highest risk for having silent myocardial ischemic events. In another prospective study of 32,068 patients without a baseline history of cancer or cardiovascular disease (69 % men: with a mean age of 46 years, and age range 26e61) over a 24-year period, evidence showed that there was an increased mortality rate predicted by blood pressure (BP) fall on standing associated with injuries and there was a higher rate of cardiovascular deaths from pronounced decreases in systolic BP during early orthostatic episodes.22 A study conducted by Rose et al followed 674 participants over a 2-year period and noted an increase in mortality rates among middleaged black and white men and woman with OH.23 This group had a 13.7% increase in mortality from ischemic strokes and heart disease, compared with a 4.2% mortality rate for those without OH. A study conducted by Ejaz et al24 showed underlying causes for 100 patients presenting to a Mayo’s clinic with OH. Their study showed that 91 patients were 60 years old or greater, 83% had significant postprandial hypotension, 84% had supine hypertension, 16% had multisystem atrophy, 13% had a malignancy, 11% had pure autonomic failure, and 7% had Parkinson’s disease.24 In several postprandial studies, the researchers showed that in healthy individual’s food lowered systolic blood pressure by only 1 mm Hg, while in patients with autonomic dysfunction, food lowered their systolic blood pressure by up to 40 mm Hg.24 26 This response is not clearly understood but is thought to be the result of an impaired baroreflexmediated response from excessive vasodilation by the splanchnicmesenteric blood supply when stimulated by food ingestion. The splanchnic-mesenteric bed accounts for up to 20%e30% of blood supply.1
235
Physiology of Standing Standing depends on having adequate blood volume, effective hemodynamic function from striated muscles, the splanchnicmesenteric vascular beds blood volume, cerebrovascular beds, and baroreflex control at the arterial and venous levels.5,12,27 Within 1 minute of standing, up to 500e1000 mL of blood pools, in the lower abdomen, buttocks, and legs.1,9,28 To prevent OH, several autonomic reflexes are activated to increase sympathetic outflow from the brainstem to the peripheral circulation to maintain BP via increasing systemic vascular resistance. Simultaneous increase in sympathetic outflow to the sinus node and withdrawal of vagal tone also prevents BP to fall by promoting reflex increase in the heart rate to maintain cardiac output despite the fall in stroke volume. These reflexes are mediated by baroreceptors, which are sensitive to changes in plasma volume (cardiopulmonary baroreceptors) or arterial pressure (arterial baroreceptors). The cardiopulmonary or low pressure baroreceptors are located in the left atrium, left ventricle, and pulmonary veins. The arterial baroreceptors are located in the carotid sinus and aortic arch.13 Thus, excessive fall in BP upon standing could be related to (1) volume depletion or inappropriate peripheral vasodilation from variety of conditions in the presence of intact autonomic function (hyperadrenergic OH) or (2) primary abnormalities in the neural control of BP (ie, neurogenic OH). The simple way to separate nonneurogenic from neurogenic OH is to determine changes in the heart rate during postural changes. Generally, failure of heart rate to increase at least 15 beats/min upon standing usually indicates the presence of neurogenic OH (Figure 1).29 Diagnostic Tests Once neurogenic OH is detected, a careful comprehensive neurology and cardiovascular history should be taken and physical examination should be completed to determine the causes of OH and guide appropriate tests to confirm diagnosis. Lesions that produce neurogenic OH may occur at the 3 different sites: (1) afferent baroreceptors, (2) central nervous system, or (3) postganglionic efferent sympathetic fibers (Figure 1). Patients with baroreflex failure often have a history of carotid sinus nerve injury from bilateral carotid endarterectomy, carotid tumor, or radiation to the neck and chest.30 In these patients, BP may become very labile and tends to be very high during stressful situations and very low during rest or dehydration because of loss of baroreflex buffering of sudden changes in BP. Patients with lesions in the postganglionic sites may have history of systemic diseases that affect efferent sympathetic fibers, such as diabetes mellitus, amyloidosis, or malignancy causing paraneoplastic autonomic neuropathy. In a small group of patients, degeneration of the postganglionic efferent fibers may occur in isolation without any systemic disease, which is known as pure autonomic failure. In contrast, patients with central nervous system disorders which produce OH often have variety of neurologic sign and symptoms, including movement disorders from multisystem atrophy or motor weakness from brainstem stroke. Patients with Parkinson’s disease are also known to have movement disorders indistinguishable from multisystem atrophy. However, the main site of lesion thought to produce OH is in the postganglionic site.31 Furthermore, many tricyclic antidepressants, which is often prescribed not only for depression, but also insomnia, may potentiate OH by acting at the brainstem centers to inhibit central sympathetic outflow with longterm use.32 Initial diagnostic tests will depend on the patient’s presenting symptoms and existing comorbidity conditions. Depending on the severity of OH, an ambulatory blood pressure monitor may be worn
236
D. Arbique et al. / JAMDA 15 (2014) 234e239
Fig. 1. Evidence-based diagnostic clinical guideline for neurogenic orthostatic hypotension (content subsumed from reference material listed in this article).
for up to 72 hours to help detect the severity of blood pressure swings that will help identify blunted nocturnal dipping or even reversed dipping. This data is vital for offering effective individualized treatment options.1,33 There are several simple office visit tests taking postural blood pressure measurements, constant electrocardiogram monitoring during postural changes and a cold pressure test by immersing a patients’ hand in ice water for 2 minutes. While patients with baroreceptor lesions are more prone to have augmented BP response to cold pressor test, patients with disorders in the central nervous system or efferent sympathetic fiber sites have very blunted, if any (
JAMDA journal homepage: www.jamda.com
Review
Management of Neurogenic Orthostatic Hypotension Debbie Arbique DNP, FNP-C, RN, CEN, CFN a, Dennis Cheek PhD, RN b, Mark Welliver DNP, CRNA, ARNP b, Wanpen Vongpatanasin MD, FAHA, FACC a, * a b
UT Southwestern Medical Center at Dallas, Internal Medicine, Cardiology Division: Hypertension Section, Dallas, TX Harris College of Nursing and Health Sciences and School of Nurse Anesthesia, Texas Christian University, Fort Worth, TX
a b s t r a c t Keywords: Neurogenic orthostatic hypotension physiology and pathophysiology with standing supine hypertension neurogenic diagnostic tests pharmacological and nonpharmacological mortality morbidity
The burden of orthostatic hypotension (OH) on public health is a universally recognized enigmatic clinical condition that is associated with significant increases on morbidity and mortality rates, and can take a major toll on one’s quality of life. Orthostatic hypotension is predictive of vascular deaths from acute myocardial infarction, strokes in the middle aged population, and increases mortality rates when associated with diabetes, hypertension, Parkinson’s disease, and patients receiving renal dialysis. The consensus definition for OH is a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 minutes of quiet standing. Because neurogenic OH is often accompanied by supine hypertension, the treatment program should aim toward minimizing OH and the potential fall injuries related to cerebral hypoperfusion without exacerbating nocturnal hypertension that may lead to excessive cardiovascular complications. Ó 2014 - American Medical Directors Association, Inc. All rights reserved.
Orthostatic hypotension (OH) in the aging population is a major burden on the public healthcare system. While the incidence of OH is low in the general population (about 0.5% incidence), there is a 30% incidence in the aging population starting after 60 years of age and up to 64% incidence in nursing home settings.1,2 OH is a dynamic state that is not a disease or a pathologic entity in itself, but rather it is a physical sign.3 The consensus definition for OH is a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 minutes of quiet standing.4 6 OH is predictive of vascular deaths from acute myocardial infarction and strokes in the middle aged population.5,7 Neurogenic OH is a more complex form of OH involving the central nervous system. Neurogenic OH is well associated with increased mortality rates for diabetes, hypertension, Parkinson’s disease, and patients receiving renal dialysis.5,8,9 Many studies divide neurogenic OH into 2 subcategories; a patient can be symptomatic or asymptomatic during OH episodes.1,4,10 Symptomatic OH usually occurs during postural changes, prolonged motionless standing, stressful events, dehydration, time of day, alcohol ingestion, carbohydrateheavy meals, heat exposure or fever, or valsalva maneuvers from straining. Symptoms include dizziness, lightheadedness, faintness,
The authors declare no conflicts of interest. * Address correspondence to Wanpen Vongpatanasin, MD, FAHA, FACC, UT Southwestern Medical Center at Dallas, Internal Medicine, Cardiology Division: Hypertension Section, 5323 Harry Hines Blvd, Dallas, TX 75390-8586. E-mail address: [email protected] (W. Vongpatanasin).
syncope episodes, inability to stand or walk, neck pain, chest pain, and cognitive impairment. Dizziness and syncope events account for up to 21% of patients presenting to the emergency department.3 In the United States, syncope related events are the sixth most common cause for hospitalizations for individuals 65 years of age or older.11 While asymptomatic patients do not show symptoms, they are at high risk for neurologic or cardiovascular events.12 Patients with supine hypertension can also exhibit OH, and the prevalence of OH in elderly hypertensive patients is 10%e30%.4,13 While there are many research publications and book chapters written on best evidence-based approaches to care for neurogenic OH patients, this valuable information has not been formally translated or disseminated into clinical practice.
Review of Literature The burden of OH on public health is a universally recognized enigmatic clinical condition that is associated with significant increases in morbidity and mortality rates, that can take a major toll on one’s quality of life1,8,14 17 A comprehensive literature review searched for evidence-based clinical practice on the topic of neurogenic OH by using Medline databases of Academic Search Premier, PubMed, OVID, Cochrane, and CINAHL. The key search words “orthostatic hypotension” were used in conjunction with the following terms and phrases for the literature search: “physiology of standing,” “pathophysiology with
1525-8610/$ - see front matter Ó 2014 - American Medical Directors Association, Inc. All rights reserved. http://dx.doi.org/10.1016/j.jamda.2013.10.014
D. Arbique et al. / JAMDA 15 (2014) 234e239
standing,” “pathophysiology of neurogenic orthostatic hypotension and supine hypertension,” “neurogenic (orthostatic hypotension) diagnosis,” “diagnostic tests,” “pharmacological management,” “nonpharmacological management,” and mortality and morbidity. All literature published within the past 35 years was considered for review. Articles that specifically addressed the key terms in their title had their abstract reviewed. Over 300 abstracts were reviewed, and 67 articles were retrieved in full based on usefulness to develop clinical guidelines for the management of orthostatic hypotension.
Epidemiology A multicenter observational, longitudinal study conducted by Rutan of 5201 men and women aged 65 years or older showed the prevalence of symptomatic OH to be 14.8% higher compared with younger age groups with a noted increase to 26% in those 85 years and older.18 This finding was statistically significant demonstrating a strong association between OH and aging. In 2008, persons 65 years or older was 38.9 million, which represents 12.8% of the US population (1 in every 8 Americans) and by 2030, the aging population is expected to grow to by 20%, to reach 71.5 million.19 In another longitudinal study conducted by Eigenbrodt et al from 1987e1996, 11,707 persons were followed who were stroke free and without overt heart disease at baseline over an 8-year period.20 The study identified a higher incidence of stroke in patients with OH compared with those without OH. The study also revealed an increased incidence for having a stroke being linked to the degrees of severity of systolic or diastolic OH, and there was a strong association with hypertension, diabetes, or Parkinson’s disease. In a prospective study, Ko et al21 supported these findings for patients having diabetes and neurogenic autonomic OH, were at a much higher risk for future ischemic stroke events. Vinik et al 7 conducted a meta-analysis of 42 published studies from 1960 to 1998 that showed diabetic patients with autonomic failure were at the highest risk for having silent myocardial ischemic events. In another prospective study of 32,068 patients without a baseline history of cancer or cardiovascular disease (69 % men: with a mean age of 46 years, and age range 26e61) over a 24-year period, evidence showed that there was an increased mortality rate predicted by blood pressure (BP) fall on standing associated with injuries and there was a higher rate of cardiovascular deaths from pronounced decreases in systolic BP during early orthostatic episodes.22 A study conducted by Rose et al followed 674 participants over a 2-year period and noted an increase in mortality rates among middleaged black and white men and woman with OH.23 This group had a 13.7% increase in mortality from ischemic strokes and heart disease, compared with a 4.2% mortality rate for those without OH. A study conducted by Ejaz et al24 showed underlying causes for 100 patients presenting to a Mayo’s clinic with OH. Their study showed that 91 patients were 60 years old or greater, 83% had significant postprandial hypotension, 84% had supine hypertension, 16% had multisystem atrophy, 13% had a malignancy, 11% had pure autonomic failure, and 7% had Parkinson’s disease.24 In several postprandial studies, the researchers showed that in healthy individual’s food lowered systolic blood pressure by only 1 mm Hg, while in patients with autonomic dysfunction, food lowered their systolic blood pressure by up to 40 mm Hg.24 26 This response is not clearly understood but is thought to be the result of an impaired baroreflexmediated response from excessive vasodilation by the splanchnicmesenteric blood supply when stimulated by food ingestion. The splanchnic-mesenteric bed accounts for up to 20%e30% of blood supply.1
235
Physiology of Standing Standing depends on having adequate blood volume, effective hemodynamic function from striated muscles, the splanchnicmesenteric vascular beds blood volume, cerebrovascular beds, and baroreflex control at the arterial and venous levels.5,12,27 Within 1 minute of standing, up to 500e1000 mL of blood pools, in the lower abdomen, buttocks, and legs.1,9,28 To prevent OH, several autonomic reflexes are activated to increase sympathetic outflow from the brainstem to the peripheral circulation to maintain BP via increasing systemic vascular resistance. Simultaneous increase in sympathetic outflow to the sinus node and withdrawal of vagal tone also prevents BP to fall by promoting reflex increase in the heart rate to maintain cardiac output despite the fall in stroke volume. These reflexes are mediated by baroreceptors, which are sensitive to changes in plasma volume (cardiopulmonary baroreceptors) or arterial pressure (arterial baroreceptors). The cardiopulmonary or low pressure baroreceptors are located in the left atrium, left ventricle, and pulmonary veins. The arterial baroreceptors are located in the carotid sinus and aortic arch.13 Thus, excessive fall in BP upon standing could be related to (1) volume depletion or inappropriate peripheral vasodilation from variety of conditions in the presence of intact autonomic function (hyperadrenergic OH) or (2) primary abnormalities in the neural control of BP (ie, neurogenic OH). The simple way to separate nonneurogenic from neurogenic OH is to determine changes in the heart rate during postural changes. Generally, failure of heart rate to increase at least 15 beats/min upon standing usually indicates the presence of neurogenic OH (Figure 1).29 Diagnostic Tests Once neurogenic OH is detected, a careful comprehensive neurology and cardiovascular history should be taken and physical examination should be completed to determine the causes of OH and guide appropriate tests to confirm diagnosis. Lesions that produce neurogenic OH may occur at the 3 different sites: (1) afferent baroreceptors, (2) central nervous system, or (3) postganglionic efferent sympathetic fibers (Figure 1). Patients with baroreflex failure often have a history of carotid sinus nerve injury from bilateral carotid endarterectomy, carotid tumor, or radiation to the neck and chest.30 In these patients, BP may become very labile and tends to be very high during stressful situations and very low during rest or dehydration because of loss of baroreflex buffering of sudden changes in BP. Patients with lesions in the postganglionic sites may have history of systemic diseases that affect efferent sympathetic fibers, such as diabetes mellitus, amyloidosis, or malignancy causing paraneoplastic autonomic neuropathy. In a small group of patients, degeneration of the postganglionic efferent fibers may occur in isolation without any systemic disease, which is known as pure autonomic failure. In contrast, patients with central nervous system disorders which produce OH often have variety of neurologic sign and symptoms, including movement disorders from multisystem atrophy or motor weakness from brainstem stroke. Patients with Parkinson’s disease are also known to have movement disorders indistinguishable from multisystem atrophy. However, the main site of lesion thought to produce OH is in the postganglionic site.31 Furthermore, many tricyclic antidepressants, which is often prescribed not only for depression, but also insomnia, may potentiate OH by acting at the brainstem centers to inhibit central sympathetic outflow with longterm use.32 Initial diagnostic tests will depend on the patient’s presenting symptoms and existing comorbidity conditions. Depending on the severity of OH, an ambulatory blood pressure monitor may be worn
236
D. Arbique et al. / JAMDA 15 (2014) 234e239
Fig. 1. Evidence-based diagnostic clinical guideline for neurogenic orthostatic hypotension (content subsumed from reference material listed in this article).
for up to 72 hours to help detect the severity of blood pressure swings that will help identify blunted nocturnal dipping or even reversed dipping. This data is vital for offering effective individualized treatment options.1,33 There are several simple office visit tests taking postural blood pressure measurements, constant electrocardiogram monitoring during postural changes and a cold pressure test by immersing a patients’ hand in ice water for 2 minutes. While patients with baroreceptor lesions are more prone to have augmented BP response to cold pressor test, patients with disorders in the central nervous system or efferent sympathetic fiber sites have very blunted, if any (
