Orthostatic Intolerance Workup

Updated: Nov 13, 2019
  • Author: Julian M Stewart, MD, PhD; more...
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Orthostatic Stress Tests

Perhaps the best “test” is medical history, which can often diagnose OI based on symptoms relieved by recumbence. Orthostatic stress tests supplement history by evoking OI in the laboratory. The predictive value of lab-induced OI for real world OI is unclear, at least for syncope; in adults older than 40 years, tilt tests do not predict vasovagal syncope (VVS). [97] . Controlled studies have not been performed in younger patients. There is no reference standard for orthostatic testing. Standing without movement may be the most physiologic orthostatic stress, but is complicated by muscle pump activity. [98] Therefore, tilt tables are used to restrict patient movement while passively placing them upright. [99] A recent adult study of POTS compared the diagnostic accuracy of standing for 10 minutes with 60o upright tilt for 10 minutes or longer. [100] Results showed that standing after being supine for 1 hour was at least as good as 10 minute tilt; longer tiltsintroduced excessive numbers of false positives. Standing HR and BP measurements were taken at 1, 3, 5, and 10 minutes. Thus, standing tests for POTS require prior supine rest. In our hands >20 min is needed to reach fluid equilibrium. More dramatic results can be obtained by lower body negative pressure (LBNP), [101] which best simulates hemorrhage but duplicates many OI findings. A combination of LBNP with upright tilt can evoke OI - usually syncope – in everyone. Tests always include measurements of BP, HR, and rhythm, and are supplemented in research laboratories by measurements of beat-to-beat CO, CBFv, regional blood flow, blood volume, sympathetic nerve activity, synaptic norepinephrine spillover, [102] and vascular biopsy. [28]

Instrumentation that measures BP, heart rate and cardiac rhythm, cardiac output (e.g., indicator dilution, inert gas rebreathing), regional blood flow (e.g., ultrasound, venous occlusion plethysmography, impedance plethysmography), and blood volume have all been bundled with clinical tilts. Studies of sympathetic control of orthostasis in conscious humans began in earnest with the use of microneurography to measure peripheral sympathetic nerve activity. [103] Other advanced techniques using sympathetic nerve norepinephrine spillover [102] to measure the effect of adrenergic vasoconstriction on local blood flow [104] and most recently to directly assess the integrity of norepinephrine synthesis and metabolic products by vascular biopsy [105, 28] can be used to find the actual mechanism of OI in sufferers.

Tilt table procedure

Early National Aeronautics and Space Administration (NASA) experiments used a HUT test to evoke autonomic reflexes and vascular responses. This device was first used in 1986 as a clinical testing agent to evaluate syncope. The tilt table is often driven by an electrical motor (although manual tables are also available) and has a supportive footboard; this enables positioning of patients at varying angles of upright tilt. Although an angle of 90° would seem most physiologic, this usually induces excessive false-positive results (i.e., patients with no history of orthostatic intolerance who have orthostatic intolerance induced during testing). Lesser angles such as 60° or 70° are customarily used.

Clinically, the HUT table test is not a particularly accurate or repeatable test for syncope. Even without excessive angles of tilt and without pharmacologic potentiation, about 25% of adolescents with no prior fainting history faint during testing. Moreover, among people who habitually faint, approximately 25-30% do not faint during the test on a given day. Results are not repeatable in the sense that a positive or negative result on one day does not ensure a positive or negative result on another day, although some patients consistently faint. As a test for fainting, the tilt table test is fraught with error; as a stressor, it is excellent and controllable. Interestingly, and in contrast to fainters, patients with postural tachycardia syndrome (POTS) often have repeatable orthostatic stress test results. The American Heart Association now regards tilt table testing as a secondary to history and physical exam and routine cardiology testing in diagnosing simple faint.

Following a resting period, a patient is placed upright; responses are assessed over the period of tilt, usually up to 30-45 minutes, as tolerated. Often, if orthostatic tachycardia is the diagnosis sought, a 10-minute tilt is sufficient. At a minimum, BP and continuous ECG are assessed. Typically, a form of continuous BP assessment is used (e.g., finger plethysmography, arterial tonometry). Respiration is also continuously assessed and often end-tidal carbon dioxide (ETCO2). In addition, researchers have used techniques to assess peripheral, thoracic, and cerebral blood flow.

The central clinical purpose of HUT testing is to reproduce symptoms of orthostatic intolerance in a setting where hemodynamic variables can be assessed, although this is not the only purpose. Symptoms and changing physiologic signs often correlate, but the definition of orthostatic intolerance requires symptoms. If the patient's defining symptoms are not reproduced but the patient has a simple faint, the test results are often regarded as false-positive and not a sign of genuine orthostatic intolerance because healthy control subjects with no prior history of fainting may faint during testing.

Data suggest the physiology of false-positive results is itself interesting and that strict use of the term negative applied to these patients' findings may be incorrect. [15] Other patterns of hemodynamic disturbance, such as postural tachycardia and the dysautonomic response, invariably seem associated with symptoms and are more reliable indicators of chronic impairment.

LBNP test

The LBNP test, developed by NASA scientists and others as a research tool, simulates many features of orthostasis by using external negative pressure on the legs, buttocks, and lower abdomen under well-controlled conditions. Actually, LBNP most closely duplicates the findings of hemorrhages that bear similarities to orthostatic intolerance, in that central hypovolemia is induced. The authors recently demonstrated a divergent response of splanchnic volume changes induced by HUT compared with LBNP. [101] LBNP resulted in splanchnic emptying, whereas HUT caused splanchnic filling. Thoracic and leg volumes similarly changed when subjected to HUT and LBNP. Currently, LBNP is a pure research tool and is, therefore, somewhat beyond the scope of this discussion.

LBNP combined with upright tilt

Even more recently, investigators have used LBNP combined with HUT. By additively combining these stressors, virtually all subjects were made to experience some form of orthostatic intolerance. The amount of negative pressure and tilt used then defines a susceptibility to orthostatic stress. [101]

Tests as Research Tools

All of these tests have a related function as research tools to evoke the orthostatic response, which is a complex interplay among arterial baroreflex, vasculature, local factors, and the CNS. The tilt table test, therefore, is not a "black box" apparatus with positive or negative responses. Everyone responds physiologically to orthostatic challenge.

The black box approach has been popular among cardiologists using a descriptive paradigm as a way to categorize patients who faint. These cardiologists sought to compare patterns of syncope during upright tilt with cardiogenic syncope caused by electrical or mechanical events. Thus, they designated positive responses associated with primary bradycardia as cardioinhibitory, positive responses associated with primary hypotension but not bradycardia as vasodepressor, and vasovagal episodes in which both heart rate and BP fell in concert as mixed.

With input from neurologists and integrative physiologists studying a wider range of orthostatic intolerance, this paradigm for the orthostatic stress response has largely been superseded by a physiologic approach that emphasizes the responses of neurovascular and neurohumoral circulatory control mechanisms to orthostatic stress.