Canadian Journal of Cardiology 33 (2017) 1725e1728
Training/Practice
Contemporary Issues in Cardiology Practice
Orthostatic Hypotension: A Practical Approach to
Investigation and Management
Amy C. Arnold, PhD, MSCI,a,b and Satish R. Raj, MD, MSCIb,c
a
Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA
b
Autonomic Dysfunction Center, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
c
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada
ABSTRACT
The maintenance of blood pressure upon the assumption of upright
posture depends on rapid cardiovascular adaptations driven primarily
by the autonomic nervous system. Failure of these compensatory
mechanisms can result in orthostatic hypotension (OH), defined as
sustained reduction in systolic blood pressure > 20 mm Hg or diastolic
blood pressure > 10 mm Hg within 3 minutes of standing or > 60

head-up tilt. OH is a common finding, particularly in elderly pop-
ulations, associated with cardiovascular and cerebrovascular morbidity
and mortality. Therefore, it is important to identify OH in the clinical
setting. The detection of OH requires blood pressure measurements in
the supine and standing positions. A more practical approach in clinics
might be measurement of seated and standing blood pressure, but
this can produce smaller depressor responses because of reduced
gravitational stress. Heart rate responses to standing should be
concomitantly measured to assess integrity of baroreflex function.
Patients with OH can present with symptoms of cerebral hypoperfusion
on standing predisposing to syncope and falls; however, many patients
are asymptomatic. When the diagnosis of OH is established, it is
important to document potentially deleterious medications and
comorbidities and to assess for neurogenic autonomic impairment
to establish underlying causes. Treatment should be initiated in a
The assumption of upright posture induces gravitational
blood pooling in the lower extremities to reduce venous return
to the heart. In healthy individuals, cardiac output and blood
pressure (BP) are maintained upon standing because of acti-
vation of autonomic neural and hormonal reflex mechanisms
that compensate for impaired venous return. Failure of these
Received for publication May 1, 2017. Accepted May 11, 2017.
Corresponding author: Dr Satish R. Raj, Department of Cardiac Sciences,
Libin Cardiovascular Institute of Alberta, University of Calgary, GAC70
HRIC Bldg, 3280 Hospital Dr NW, Calgary, Alberta T2N 4Z6, Canada.
Tel.: þ1-403-210-6152; fax: þ1-403-210-9444.
E-mail: Satish.raj@ucalgary.ca
See page 1728 for disclosure information.
http://dx.doi.org/10.1016/j.cjca.2017.05.007
0828-282X/Ó 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

RESUM 
E
Le maintien de la pression arte rielle lors du passage à la position
debout de pend de la rapidite  des adaptations cardiovasculaires prin-
cipalement re gule
es par le système nerveux autonome. La de faillance
de ces me canismes compensatoires peut entraîner l’hypotension
orthostatique (HO), c’est-à-dire la re duction prolonge
e de la pression
arterielle systolique > 20 mm Hg ou de la pression arte rielle dia-
stolique > 10 mm Hg dans les 3 minutes suivant le passage à la
position debout ou une inclinaison de plus de 60 degre s. L’HO qui est
particulièrement fre quente chez les personnes âge es est associe e à
une morbidite  et mortalite
 cardiovasculaires et vasculaires ce
rebrales.
Par conse quent, il est important d’indentifier l’HO en milieu clinique.
Le depistage de l’HO exige la prise de mesures de la pression arte rielle
en position couche e et en position debout. Une approche qui serait
plus pratique en milieu clinique est la mesure de la pression arte rielle
en position assise et en position debout, mais cela peut entraîner des
ponses vaso-de
re pressives plus petites en raison de la re duction de
l’effet gravitationnel. Des mesures de la re ponse de la frequence
cardiaque à la position debout devraient être prises de manière con-
comitante pour e valuer l’inte
grite
 de la fonction barore
flexe. Les pa-
tients souffrant d’HO peuvent pre senter des symptômes
d’hypoperfusion ce rebrale en position debout qui les pre
disposent à la
compensatory mechanisms can result in orthostatic hypoten-
sion (OH), or low BP upon standing (Fig. 1). OH is defined
as a sustained reduction of at least 20 mm Hg in systolic BP or
10 mm Hg in diastolic BP within 3 minutes of standing or
> 60
head-up tilt.1 Patients with OH often experience
symptoms of cerebral hypoperfusion including lightheaded-
ness, dizziness, blurred vision, fatigue, and headache. The
etiology of OH is multifactorial and can include non-
neurogenic and neurogenic causes. OH can occur in other-
wise healthy people when faced with severe hypovolemic or
vasodilatory stress, although it is more common in people
with some underlying neurovascular pathology. The incidence
of OH increases with age affecting 5%-16% of middle-aged
and elderly community dwellers, and more than 50% of
elderly patients in nursing homes and geriatric wards.2 OH
1726
structured and stepwise approach starting with nonpharmacological
interventions (eg, lifestyle modifications and physical counter-
manoeuvres), and adding pharmacological interventions as needed in
patients with severe OH (eg, midodrine, droxidopa, fludrocortisone).
The treatment goal in OH should be to improve symptoms and func-
tional status, and not to target arbitrary blood pressure values.
contributes substantially to risk of falls, disability, and
impaired quality of life.2,3 The presence of OH is also asso-
ciated with numerous comorbidities (eg, hypertension,
chronic kidney disease, cognitive impairment), and is an in-
dependent risk factor for cardiovascular, cerebrovascular, and
all-cause morbidity and mortality.2 Because of the increasing
aging population worldwide and potential effect of OH-
related hospitalizations,3 it is critical to identify and treat
this condition in clinical practice.
Clinical Assessment of OH
Initial assessment for OH should include BP and heart rate
measurements after the patient has been supine (> 5 mi-
nutes), and again after 1 and 3 minutes of standing.1 Passive
head-up tilt table testing to an angle > 60
can also be used to
detect OH, but can produce false positive results particularly
in elderly patients because of vasovagal reactions. In clinic
settings, BP is often only measured in the seated position.
Although because of practical limitations, this results in OH
being undetected in most patients. An alternative approach is
measurement of BP changes from the seated to standing po-
sition, which does not require a bed and thus might be more
easily performed in clinics.4 Because this sit to stand testing
produces smaller depressor responses because of reduced
gravitational stress, a decrease in systolic BP > 15 mm Hg or
diastolic BP > 7 mm Hg should be used as the diagnostic
threshold.4 OH detection might require measurement of BP
over several days. In these cases, patients should maintain a BP
diary with recording of orthostatic vital signs at different times
of the day and after stressors (eg, medications, meals, exercise).
The most sensitive and consistent measurements are usually
obtained early in the morning when patients are most
symptomatic because of nocturnal pressure natriuresis.
Asymptomatic OH with intact cerebral autoregulation is a
common occurrence; however, these patients should still be
considered at risk for falls and syncope. Finally, ambulatory
BP monitoring might be useful to detect OH and related
comorbidities (eg, supine hypertension, postprandial hypo-
tension), but only in patients able to record postural changes.
When the diagnosis of OH has been established, a detailed
history and physical examination should be performed to
document medications, comorbidities, and symptoms. Idio-
pathic OH is common with advanced age because of arterial
stiffness and reductions in baroreceptor reflex sensitivity,
muscle pump activity, and a1-adrenergic vasoconstriction.1,2
Canadian Journal of Cardiology
Volume 33 2017
syncope et aux chutes. Toutefois, plusieurs patients sont asympto-
matiques. Lorsque le diagnostic de HO est e tabli, il est important de
pertorier les me
re dicaments potentiellement de  le
tères et les
comorbidite s, puis d’e
valuer le système nerveux autonome pour e tablir
les causes sous-jacentes. Le traitement devrait être amorce  selon une
approche structure e et progressive en commençant par les in-
terventions non pharmacologiques (par ex. les modifications du mode
de vie et les manœuvres de contre-pression physique) et l’ajout d’in-
terventions pharmacologiques si ne cessaire chez les patients ayant
une HO importante (par ex. la midodrine, le droxidopa, la flu-
drocortisone). L’objectif du traitement de l’HO devrait consister à
ame liorer les symptômes et l’e tat fonctionnel, et ne pas cibler des
valeurs arbitraires de la pression arte rielle.
Additional causes of OH include side effects of medications,
anemia, volume loss (eg, dehydration, severe vomiting, or
diarrhea), physical deconditioning, benign infections (eg,
urinary tract infection), and systemic diseases involving
autonomic nerves (eg, amyloidosis, diabetes mellitus, Par-
kinson disease).1,2 Exaggerated orthostatic tachycardia might
suggest volume depletion or these other secondary causes.
Patients with acute or subacute onset of OH and severe
presyncopal symptoms should be evaluated for autoimmune
or paraneoplastic syndromes. In rare cases, patients with OH
have a primary neurodegenerative disorder (eg, multiple sys-
tem atrophy, pure autonomic failure, Lewy body dementia).
These patients often present with severe OH and lack of
compensatory heart rate increase with standing (< 15 bpm).
Standardized autonomic function testing is recommended to
confirm diagnosis of primary neurodegenerative disorders
associated with OH.5
Treatment of OH
Treatment of OH should involve a structured stepwise
approach, which might include nonpharmacological as well as
pharmacological interventions (Table 1).2 The treatment goal
for OH patients is to improve symptoms and functional
status, and not to achieve target BP values. The need for
treatment should be determined on an individual basis with
consideration given for OH severity and presence of comor-
bidities. Patients should maintain a diary of symptoms and
orthostatic vital signs to help assess treatment efficacy. There is
limited evidence to guide OH treatment, and recommenda-
tions are often on the basis of small cross-sectional trials with
acute interventions in neurogenic OH.5 Potential limitations
are that these previous studies might not reflect the more
common idiopathic OH, have not been validated in large
controlled clinical trials, and have not evaluated long-term
treatment efficacy.
Nonpharmacological
Medications known to aggravate OH should be dis-
continued when appropriate. Because OH patients are
preload-dependent, nitrates and diuretics should be stopped.
Other medications that might worsen or contribute to OH
can include dopaminergic drugs, anticholinergic drugs,
tricyclic antidepressants, a1-blockers (eg, tamsulosin), and
antihypertensive medications.2 Discontinuation of antihy-
pertensive medications, however, should be approached with
Arnold and Raj
Detection and Treatment of OH
Figure 1. Head-up tilt table test in a patient with orthostatic hypo-
tension showing instantaneous heart rate (top) and blood pressure
trace (bottom). At baseline, the heart rate is around 75 bpm, and the
blood pressure is around 120/65 mm Hg. Immediately with the onset
of head-up tilt at 70
(vertical line), the systolic blood pressure and
diastolic blood pressure both decrease, with a narrowing of the pulse
pressure (bottom). There is also a small, but blunted, increase in
heart rate (top).
caution for several reasons. First, although a relationship has
been established with use of sympatholytics (eg, a- and
b-adrenergic antagonists), the association of other antihyper-
tensive medications with OH is uncertain. Second, studies
have shown an increased fall risk in elderly patients with
uncontrolled hypertension. Finally, withholding antihyper-
tensive medications can worsen OH by promoting pressure
diuresis. Therefore, judicious use of short-acting antihyper-
tensive medications is recommended in patients with OH
with close monitoring of orthostatic vital signs and symptoms.
Nonpharmacological approaches should then be initiated
as first-line treatment and include physical counter-
manoeuvres and lifestyle modifications (Table 1). Patients
should be educated on use of physical countermanoeuvres to
reduce venous pooling such as changing positions gradually,
leg-crossing, squatting, and active tensing of leg muscles.
Breathing-related countermanoeuvres might also benefit
cardiovascular stability in OH patients through actions on the
respiratory pump to facilitate venous return to the heart from
the abdomen and upper extremities. These respiratory ma-
noeuvres include slow deep breathing and creation of inspi-
ratory resistance through use of an impedance threshold
device, inspiratory sniffing, or inspiration through pursed lips.
1727
Table 1. Treatment approaches in orthostatic hypotension
Nonpharmacological interventions
Reduce venous pooling
 Physical countermanoeuvres (eg, standing with legs crossed, squatting,
active tensing of leg muscles, breathing-related manoeuvres to increase
inspiratory resistance, and avoiding getting up too quickly or standing
motionless)
 Compression stockings or abdominal binders (30-40 mm Hg)
Increase central volume
 Increase sodium intake (6-9 g/d)
 Increase water intake (2-3 L/d)
 Raise head of bed during night to prevent pressure natriuresis
(6-9 inches)
Other lifestyle modifications
 Eat small frequent meals
 Physical activity such as water exercise, recumbent bicycling, or rowing
 Avoid alcohol consumption
 Avoid situations that increase core body temperature such as prolonged
hot showers
Pharmacological interventions
Increase intravascular volume
 Fludrocortisone (0.1-0.2 mg/d, PO)
Increase vascular resistance
 Midodrine (2.5-10 mg, PO)
 Droxidopa (100-600 mg, PO)
 Atomoxetine (18 mg, PO)
 Yohimbine (5.4 mg, PO)
 Pyridostigmine (60 mg, PO)
 Octreotide (12.5-25 mg, subcutaneous)
 Pseudoephedrine (30 mg, PO)
Combination therapy
 Fludrocortisone (0.1-0.2 mg/d, PO) and midodrine (5-10 mg, PO)
 Ergotamine (1 mg, PO) and caffeine (100 mg, PO)
 Midodrine (5-10 mg, PO) or pseudoephedrine (30 mg, PO) and water
(500 mL)
PO, orally.
Custom-fitted thigh or waist-high compression stockings and
abdominal binders also reduce venous pooling to improve
orthostatic tolerance, when graded pressures of at least
30-40 mm Hg are applied. To improve central volume,
increased ingestion of sodium (6-10 g/d) and water (2-3 L/d)
is recommended. Rapid ingestion of plain water also serves as
a rescue measure in OH (500 mL ingested within 2-3 mi-
nutes), by eliciting a sympathetic nervous system-mediated BP
elevation for 60-90 minutes. In patients with supine hyper-
tension, elevating the head of the bed (6-9 inches) reduces
nocturnal pressure natriuresis to attenuate morning volume
depletion. In terms of lifestyle modifications (Table 1),
patients should engage in physical activity as tolerated to avoid
deconditioning, avoid alcohol, eat small frequent meals to
prevent postprandial hypotension, and avoid situations that
increase core body temperature to elicit peripheral vasodila-
tion. These nonpharmacological approaches are cost-effective
and can be safely combined with pharmacological
interventions; however, there is often poor compliance.
Pharmacological
The use of additional pharmacological interventions might
be necessitated in patients with severe OH, when non-
pharmacological approaches are insufficient to prevent pre-
syncopal symptoms (Table 1).2,5 Pharmacological treatment is
unlikely to improve outcomes in asymptomatic patients. The
presence of hypertension and underlying cardiovascular dis-
ease must also be considered.
1728
In patients with hypertension or cardiovascular disease,
short-acting pressor agents to increase vascular resistance are
preferred. Midodrine was approved by the US Food and Drug
Administration for symptomatic OH and improved ortho-
static tolerance in controlled clinical trials.5 Midodrine is a
prodrug whose metabolite desglymidodrine stimulates
a1-adrenoreceptors in blood vessels to increase vascular
resistance. Because midodrine has a short half-life, it can be
given as needed 30-45 minutes before upright activities
(2.5-10.0 mg orally every 4 hours 3 times per day). Caution is
recommended in patients with congestive heart failure and
renal failure. Side effects include piloerection, scalp pruritus,
and urinary retention. Patients should avoid the supine
position within 5 hours of taking midodrine because of the
risk of supine hypertension (so it should not be dosed within
4-5 hours of bedtime). Nominal dosing times are 8 AM,
12 PM, and 4 PM.
More recently, the US Food and Drug Administration
approved droxidopa for neurogenic OH treatment in the
United States (not available in Canada). Droxidopa is a
synthetic prodrug that is converted to norepinephrine in the
brain and peripheral tissues. Circulating norepinephrine
levels are maximally increased at 6 hours after droxidopa
dosing, with persistent elevation for 46 hours. Droxidopa is
well tolerated and improved orthostatic tolerance in
controlled trials in neurogenic OH (100-600 mg orally, 3
times per day). Similar to midodrine, droxidopa should not
be taken within 5 hours of bedtime. Caution is recom-
mended in patients with congestive heart failure and chronic
renal failure and side effects include headache, dizziness,
nausea, and fatigue.
In patients without hypertension or heart failure,
fludrocortisone (0.1-0.2 mg/d) is considered first-line phar-
macotherapy. Fludrocortisone acts at renal mineralocorticoid
receptors to promote sodium and water retention and thus
increase intravascular volume. Long-term BP effects of flu-
drocortisone, however, are attributed to enhanced blood vessel
sensitivity to pressor hormones such as norepinephrine and
angiotensin II. Patients should be monitored for headaches,
volume overload, and hypokalemia. Chronic fludrocortisone
can also exacerbate supine hypertension and contribute to end
organ damage.
Canadian Journal of Cardiology
Volume 33 2017
Other medications have shown treatment efficacy in
neurogenic OH including pseudoephedrine, atomoxetine
(norepinephrine reuptake inhibitor), yohimbine (a2-adrenergic
receptor antagonist), pyridostigmine (cholinesterase
inhibitor), and octreotide (somatostatin analogue; Table 1).
Patients refractory to individual treatments might benefit from
combination therapy including fludrocortisone with mido-
drine, ergotamine with caffeine, midodrine or pseudoephe-
drine with water bolus, and yohimbine with atomoxetine
(Table 1). If patients are unresponsive to these treatment
options, referral to a specialized autonomic centre might be
necessary.
Funding Sources
This work was supported by the National Institutes of
Health (HL122507).
Disclosures
S.R.R. is a consultant for Lundbeck NA Ltd and GE
Healthcare, and receives research support from the Canadian
Institutes of Health Research, the Cardiac Arrhythmia
Network of Canada, and Medtronic Inc. A.C.A. has no
conflicts of interest to disclose.
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