Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

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Consensus statement on the definition of orthostatic hypotension, neurally mediated
syncope and the postural tachycardia syndrome
Roy Freeman⁎, Wouter Wieling, Felicia B. Axelrod, David G. Benditt, Eduardo Benarroch, Italo Biaggioni,
William P. Cheshire, Thomas Chelimsky, Pietro Cortelli, Christopher H. Gibbons, David S. Goldstein,
Roger Hainsworth, Max J. Hilz, Giris Jacob, Horacio Kaufmann, Jens Jordan, Lewis A. Lipsitz,
Benjamin D. Levine, Phillip A. Low, Christopher Mathias, Satish R. Raj, David Robertson, Paola Sandroni,
Irwin J. Schatz, Ron Schondorf, Julian M. Stewart, J. Gert van Dijk
1. Introduction
In 1996, following a multi-specialty Consensus Conference
sponsored by the American Academy of Neurology and the American
Autonomic Society, a brief definition of orthostatic hypotension was
published. This definition has been widely used and has withstood the
test of time. Fifteen years later, advances in the understanding of
orthostatic hypotension and disorders of orthostatic tolerance have
made it necessary to clarify and expand the earlier definition. In this
updated consensus statement, endorsed by the American Autonomic
Society, the European Federation of Autonomic Societies, the
Autonomic Research Group of the World Federation of Neurology
and the Autonomic Disorders section of the American Academy of
Neurology, we refine and update the definition, pathophysiology and
clinical features of orthostatic hypotension. We also add the
definitions of two highly prevalent disorders of orthostatic tolerance,
neurally mediated (reflex) syncope and the postural tachycardia
syndrome. This update is the product of a group of experts in the field
but is not an evidence based clinical guideline.
2. Orthostatic hypotension
2.1. Definition
Orthostatic hypotension is a sustained reduction of systolic blood
pressureof at least 20 mm Hg or diastolic blood pressureof 10 mm Hg
within 3 min of standing or head-up tilt to at least 60° on a tilt table.
Orthostatic hypotension is a clinical sign and may be symptomatic or
asymptomatic. In patients with supine hypertension, a reduction in
systolic blood pressure of 30 mm Hg may be a more appropriate
criterion for orthostatic hypotension because the magnitude of the
orthostatic blood pressure fall is dependent on the baseline blood
pressure.
2.2. Pathophysiology
Immediately after standing, there is gravitationally mediated
redistribution of the blood volume, and a pooling of 300 to 800 ml
of blood in the lower extremities and splanchnic venous capacitance
system. As a consequence, venous return to the heart falls and cardiac
filling pressure is reduced. This results in diminished stroke volume
and cardiac output. In response, sympathetic outflow to the heart and
blood vessels increases and cardiac vagal nerve activity decreases.
These autonomic adjustments increase vascular tone, heart rate and
cardiac contractility, and stabilize arterial pressure. During standing,
contraction of the lower body skeletal muscle prevents excessive
pooling and augments venous return to the heart.
Orthostatic hypotension is caused by an excessive fall of cardiac
output or by defective or inadequate vasoconstrictor mechanisms. The
focusofthisconsensusstatementisneurogenicorthostatichypotension,
i.e.,orthostatichypotensionduetoinadequatereleaseofnorepinephrine
from sympathetic vasomotor neurons leadingto vasoconstrictor failure.
2.3. Epidemiology
Orthostatic hypotension occurs in patients with neurodegenerative
disorderssuchasmultiplesystematrophy,Parkinson'sdiseaseandpure
autonomic failure and in individuals with peripheral neuropathies and
ganglionopathies that affect the autonomic nerves. The prevalence of
orthostatic hypotension increases with age. Orthostatic hypotension is
more common in institutionalized (up to 70%) than community
dwelling elderly (~6%).
2.4. Clinical features
Characteristic symptoms include lightheadedness, dizziness, pre-
syncope and syncope. Loss of consciousness is usually of gradual onset
but may occur suddenly. Some patients present with more general
complaints such as weakness, fatigue, cognitive slowing, leg buckling,
visual blurring, headache, neck pain, orthostatic dyspnea or chest
pain.
Autonomic Neuroscience: Basic and Clinical 161 (2011) 46–48
⁎ Corresponding author at: Autonomic and Peripheral Nerve Laboratory, Department
of Neurology, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA
02215, U.S.A. Tel./fax: +1 617 632 8454.
E-mail address: rfreeman@bidmc.harvard.edu (R. Freeman).
1566-0702/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.autneu.2011.02.004
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2.5. Confounding variables
Several confounding variables may influence the extent of the
orthostatic blood pressure fall.
2.5.1. Supine hypertension
Many patients with neurogenic orthostatic hypotension have
supine hypertension even before treatment of hypotension is
initiated. Some of these patients have blood pressure falls on standing
that fulfill criteria for orthostatic hypotension although blood
pressure remains at or above normal range. The clinical significance
of this phenomenon is not known.
2.5.2. Diurnal variability
Orthostatic hypotension is more common and more severe in the
morning. This phenomenon is most likely due to high supine
nocturnal blood pressure which causes a pressure diuresis and results
in intravascular volume depletion over night. Redistribution of
intravascular volume also may contribute to diurnal variability.
2.5.3. Food ingestion
Patients with autonomic failure and the elderly are susceptible to
significant falls in blood pressure associated with meals. This is
exacerbated by large meals, meals high in carbohydrate, and alcohol
intake.
2.5.4. Age
The orthostatic blood pressure fall increases with age in many
elderly individuals. This is due to several factors including supine
hypertension,ageassociatedchangesinbaroreflexfunction,inadequate
vasoconstrictor responses, reduced cardiac and vascular compliance,
decreased blood volume and lesser efficiency of the skeletal muscle
pump.
2.5.5. Medications
Diuretics, sympatholytic agents and other vasodilators may
increase the postural blood pressure fall. Such medications include
blood pressure lowering medications, antidepressants (particularly
tricyclic agents) and certain anti-Parkinsonian agents.
2.5.6. Other variables
The orthostatic blood pressure fall is also influenced by hydration,
cardiacandvascularstiffness,ambienttemperature,gender,prolonged
recumbency and deconditioning.
2.6. Variants
2.6.1. Initial orthostatic hypotension
An exaggerated transient fall in blood pressure may occur shortly
upon standing accompanied by symptoms of hypoperfusion. Initial
orthostatic hypotension is defined as a transient blood pressure
decrease (N40 mm Hg systolic blood pressure and/or N20 mm Hg
diastolic blood pressure) within 15 s of standing. This blood pressure
fall, which occurs in both old and young subjects, is observed with
continuous beat-to-beat blood pressure monitoring. It may occur
during active standing and to a lesser degree with passive tilting. This
may be a common unrecognized cause of syncope. The underlying
pathophysiology is thought to be a transient mismatch between
cardiac output and peripheral vascular resistance that occurs with
rapid postural change.
2.6.2. Delayed orthostatic hypotension
Some patients present with symptomatic orthostatic hypotension
that occurs beyond three minutes of standing. The clinical significance
of delayed orthostatic hypotension is unknown. These delayed falls in
blood pressure may be a mild or early form of sympathetic adrenergic
failure. This disorder may be revealed in patients with suspected
orthostatic hypotension by extending the period of orthostatic stress
(head-up tilt or stand) beyond 3 min.
3. Neurally mediated (reflex) syncope
3.1. Definitions
3.1.1. Syncope and transient loss of consciousness
There are several different mechanisms that result in transient loss
of consciousness. Causes may be traumatic or nontraumatic; the latter
include syncope, epileptic seizures, metabolic disorders, and very
rarelya transientischemicattackin theposteriorcirculation. Theterm
syncope indicates a specific pathophysiology and should only be used
to describe a transient loss of consciousness and postural tone
resulting from global cerebral hypoperfusion with spontaneous and
complete recovery and no neurological sequelae. When the cause of
unconsciousness is not clear the episode should not be called syncope.
3.1.2. Neurally mediated syncope
Neurally mediated (reflex) syncope, e.g., vasovagal, situational
(cough, swallowing, micturition) or carotid sinus syncope refers to a
heterogeneous group of conditions in which there is a relatively
sudden change in autonomic nervous system activity leading to a fall
in blood pressure, heart rate and cerebral perfusion. Neurally
mediated syncope is best understood as a reflex with afferent, central
and efferent pathways. The term ‘neurocardiogenic syncope’ is
frequently used to describe reflex syncope but it should be abandoned
because the origin of the reflex is rarely in the heart.
3.2. Clinical features
Neurally mediated syncope is typically preceded by prodromal
symptoms and signs that may occur up to 60 s prior to loss of
consciousness. Prodromal features include pallor, diaphoresis, nausea,
abdominal discomfort, yawning, sighing, and hyperventilation. These
are followed by the features of cerebral and retinal hypoperfusion
such as visual and auditory disturbances, concentration difficulties
and cognitive slowing.
3.3. Pathophysiology
During neurally mediated syncope, efferent sympathetic
vasoconstrictor nerve activity decreases leading to a loss of vasoconstric-
tortoneandparasympathetic(vagal)outflowincreasescausingheartrate
slowing. The range of bradycardia varies widely in reflex syncope, from a
small reduction in peak heart rate to several seconds of asystole.
The trigger for reflex syncope can be central (e.g., emotions, pain,
blood phobia) or peripheral (e.g., prolonged orthostasis, increased
trigeminal or carotid sinus afferent activity), but the precise afferent
nerve pathways and central nervous system mechanisms involved in
reflex syncope are largely unknown.
In addition to reflex-mediated neural changes, other environmental
or physical factors frequently contribute to lower blood pressure and
diminish cerebral blood flow during reflex syncope. For example, heat
exposure leading to peripheral vasodilatation may contribute to
hemodynamic stress; straining with a closed glottis reduces venous
returnandincreasesintracranialpressure;andhyperventilation-induced
hypocapnia reduces cerebral blood flow and induces vasodilatation in
skeletal muscle. Insomeinstances,thesefactors may bethe mainreason
for the loss of consciousness.
As reflex syncope requires a reversal of the normal autonomic
outflow, it usually occurs in people with a functional autonomic
nervoussystem.Reflex syncope shouldbe distinguished fromsyncope
due to neurogenic orthostatic hypotension in patients with chronic
autonomic failure.
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3.4. Epidemiology
The prevalence of syncope in the general population is high. The
vast majority of syncope is caused by reflex syncope. The frequency of
reflex syncope increases during adolescence and in those over
55 years. Many adults with reflex syncope have had similar episodes
in their youth. In the young, orthostatic and emotional vasovagal
faints accompanied by characteristic prodromal symptoms are
common, while in the elderly, typical prodromal symptoms are less
frequent. Carotid sinus hypersensitivity, cough and defecation
syncope occur almost exclusively in the elderly.
4. Postural tachycardia syndrome
4.1. Definition
The postural tachycardia syndrome (POTS) is characterized by a
sustained heart rate increment of ≥30 beats/min within 10 min of
standing or head-uptilt in the absence of orthostatic hypotension. The
standing heart rate for all subjects is often ≥120 beats/min. These
criteria may not be applicable for individuals with low resting heart
rates. For individuals aged 12–19 years the required increment is at
least 40 beats/min. The orthostatic tachycardia may be accompanied
by symptoms of cerebral hypoperfusion and autonomic overactivity
that are relieved by recumbency.
4.2. Pathophysiology
The etiology and pathophysiology of POTS are unknown but are
likely to be heterogeneous. The syndrome is associated with
deconditioning, recent viral illness, chronic fatigue syndrome and a
limited or restricted autonomic neuropathy.
Thedifferentialdiagnosisincludesconditionsthatcausetachycardia,
such as thyrotoxicosis, inappropriate sinus tachycardia and other
cardiac rhythm abnormalities, pheochromocytoma, hypoadrenalism,
anxiety, dehydration, and medications (e.g., vasodilators, diuretics, and
ß-agonists).
4.3. Epidemiology and clinical features
TheprevalenceofPOTSisnotknown.Thesyndromeismorecommon
in women. The orthostatic symptoms consist of lightheadedness, visual
blurring or tunnel vision, palpitations, tremulousness, and weakness
(especially of the legs). Other symptoms include fatigue, exercise
intolerance, hyperventilation, shortness of breath, anxiety, chest pain,
nausea, acral coldness or pain, concentration difficulties and headaches.
On clinical examination, in addition to the heart rate increment,
pulse pressure may be reduced and acral coldness may be present.
Continued standing may lead to venous prominence, cyanosis and
foot swelling. A hyperadrenergic state is present in some patients who
have a resting tachycardia, sweating, and tremulousness.
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R. Freeman et al. / Autonomic Neuroscience: Basic and Clinical 161 (2011) 46–48