Orthostatic Intolerance Treatment & Management

Updated: Nov 13, 2019
  • Author: Julian M Stewart, MD, PhD; more...
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Medical Care

Orthostatic hypotension

Supportive care and treatment of the underlying illness are essential. Thus, in the case of dopamine-beta-hydroxylase (DBH) deficiency, droxidopa, which bypasses the missing enzyme, can provide definitive remediation. [106] It may also be the drug of choice for most neurogenic orthostatic hypotension (NOH) since it can provide norepinephrine production through alternative pathways. [107] Supportive therapy focuses on decreasing symptomatic OH and syncope. Such therapy would include physical countermaneuvers including compression garments, and dietary changes (increased salt, rapid water drinking). Supportive drug therapy often aims to increase blood volume by promoting salt and water retention (fludrocortisone) or by increasing red blood cell mass (recombinant erythropoietin). [10] Defects in erythropoietin may occur as part of the denervation in autonomic failure. [108] Short-acting pressor drugs such as midodrine or drugs that enhance autonomic activity (atomoxetine, pyridostigmine) are alsoused. [109, 10]

Rapid water ingestion of approximately 16 ounces deserves special mention. Studies in adults have demonstrated that intake of water free of solute can increase blood pressure and improve sympathetic vasoconstriction after a sufficient time has elapsed for the water to reach the small intestine, say 20 minutes. [95] The palliative effect of water encompasses all OI including OH, postural tachycardia syndrome (POTS), and vasovagal syncope (VVS) [110] and can be successfully used to prevent blood phobic vasovagal syncope. Effects last for several hours. The mechanism is dependent on osmolarity and may depend on TRPV4 C-fiber receptors within the portal system. [96] This is a very important, simple, and effective palliation that is not often considered by clinicians.

Postural tachycardia syndrome (POTS)

Therapy for neuropathic postural tachycardia syndrome (POTS) includes general supportive measures such as physical countermaneuvers, increased salt and water intake, and exercise. Pharmacotherapy has focused on improving sympathetic vasoconstriction, which unfortunately uses medications with widespread systemic effects. Midodrine, an a-1 adrenergic agonist, can be helpful and has few side effects apart from piloerection. [111, 112] Mestinon (pyridostigmine), [113] an acetylcholinesterase inhibitor, alone or in combination with midodrine, can be very helpful through its potentiation of cholinergic ganglionic nerve activity and through its muscarinic effects. There are great expectations for Droxidopa in trials being conducted outside the United States.

ß-blockers have been used in forms of hyperadrenergic POTS with variable success. [114, 115] Innovative treatment with angiotensin II receptor blockers (ARBs) is under investigation. Exercise has always been a mainstay of rehabilitation in these patients. Recent work indicates that gravitational deconditioning (e.g., bedrest) is a frequent concomitant of the illness and that a graded exercise program can be very effective in improving overall patient well-being. [114, 116]

Postural syncope (vasovagal syncope, acute OI, simple faint)

First time postural noncardiogenic fainting with no sequelae probably requires no treatment. The first time fainter rarely knows what is happening. Once suitably apprised, countermeasures can be employed. These include avoidance of precipitants and physical countermaneuvers; the most effective countermaneuvers are lying down with legs up or squatting. Both propel blood from the lower body below the diaphragm back into the central circulation. Other countermaneuvers include those that enhance the skeletal muscle pump (e.g., leg crossing) or activate the exercise pressor reflex (isometric hand grip). [73, 117, 75] Generally, enhanced salt and water intake is encouraged and has shown some efficacy in small studies employing very large amounts of salt loading. [118] Rapid water ingestion offers an effective palliative effect. Thus, once syncope patients have staved off the faint with physical maneuvers, they are counseled to consume 16 ounces of water before attempting to stand up. In olderpatients, confounding use of antihypertensives or diuretics need to be considered. Pharmacotherapy (atenelol or fludrocortisone) has not been shown to be more effective than placebo in younger patients in large multicenter studies. [119] Reports of exquisite sensitivity to midodrine are found in Chinese children [120] but are not evident in other populations. [121] We have recently shown midodrine as effective in the treatment of neuropathic, but not hyperadrenergic POTS. [112] Other pharmacologic strategies tested in small studies include selective serotonin reuptake inhibitors (SSRIs) including paroxetine, which showed efficacy in a double-blind randomized study of a select patient subset (n=68). [122] Asystolic faints have been shown to improve with pacemaker insertion. [123] Work into the fundamental molecular physiology of fainting is ongoing in our laboratory and in others. Our hope is to determine specific therapy based upon specific pathophysiology.

Vasovagal syncope (VVS)

Recurrent unexplained postural syncope due to vasovagal syncope (VVS) is not deadly unless the patient is in harm’s way. Trained athletes have increased risk of VVS compared to untrained persons. [116] Iron and even ferritin deficiency aggravates VVS. [124]

To date, no single pharmacological intervention has been proven more effective than placebo in large clinical trials of VVS. [125, 119] Placebo exerts 30-40% benefit in these studies. Salt and water supplementation can be helpful but a large amount of salt is needed. [118]

Currently, compensatory physical countermaneuvers are the recommended treatment for VVS. [76] The fainting prodrome must be recognized for countermeasures to be effective. First faints are rarely countered because patients don’t understand what's happening.

Countermaneuvers including immediate lying down or squatting cause postural VVS to cease. Prolonged prodrome counterpressure maneuvers such as leg-crossing, buttocks clenching, and fist clenching may also be effective. [126, 127] Once supine, the patient should not immediately stand. Instead, the patient should drink 16 ounces of water and remaining supine for >20 minutes following the episode.

If there is no prodrome or if there is abrupt onset with injury, then consider asystolic vasovagal faint or an arrhythmia and evaluate by loop recording electrocardiography. [54, 128]

If total loss of consciousness is not transient, it is not a faint, it is coma. VVS is less than 2 minutes of total loss of consciousness, as a matter of consensus. Rarely, fainting promotes an underlying seizure disorder via cerebral ischemia.



Enhanced salt and water intake is the common wisdom. However, evidence-based literature has only shown effect with ingestion of large quantities of salt. Research may now show a considerable effect of diet on the presence of vasoactive substances including the ingestion of excess nitrates and nitrites, but studies remain largely anecdotal.



One confounding and alarming issue is the tendency for POTS patients to become bedrested. Prolonged bedrest emulates microgravity and has deleterious effects, [129] including OI [130] reductions in blood volume and cardiac size, redistribution of blood, osteoporosis, skeletal muscle pump atrophy, and more. [131] Vasoconstriction is impaired, [132] and bedrest causes a self-perpetuating state of OI that can emulate or intensify POTS. It is paramount for POTS patients to leave bed and recondition. Well-structured exercise protocols are essential and must accommodate patients who start off bedrested. [114] Reconditioning invariably improves patient well-being. Recent work support the idea that POTS patients are also exercise deconditioned compared to matched volunteers. [133] While exercise deconditioning may or may not be causal in POTS, it is clear that exercise reconditioning is beneficial and should be advocated for all POTS patients.