Author(s): Kaitlyn DeHority, MD, Colette Piasecki-Masters, MD, Elizabeth Roux, BA, Sunil Sabharwal, MD
Originally published: July 20, 2012 Last updated: June 19, 2025
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Disease/Disorder

Definition

Orthostatic hypotension (OH) is defined as a reduction in systolic blood pressure (BP) of at least 20 mm Hg or a reduction in diastolic BP of at least 10 mm Hg within 3 minutes of standing or head-up tilting to 60 degrees.1 A smaller drop in blood pressure may be equally important when associated with relevant symptoms that indicate impaired perfusion. OH following spinal cord injury (SCI) is common and well-documented, most often seen with complete lesions above neurological level T6 and most severe during the acute phase.2,3

Etiology

SCI may cause dysregulation in the autonomic nervous system and associated reflexes. The prevalence of OH as well as the degree of the fall in blood pressure is higher with cervical when compared to thoracic injuries. Symptoms are also more common with complete over incomplete injuries. Low plasma volume, hyponatremia, decreased baroreflex function, and cardiovascular deconditioning may be additional contributing factors in some instances.3

Epidemiology including risk factors and primary prevention

OH has been reported to be more common after traumatic than nontraumatic SCI. Prevalence in acute SCI has been reported to be as high as 74% and occurs more frequently with tetraplegia than paraplegia.3,4 Symptoms are less likely to occur in SCI below the origin of the major splanchnic outflow at T6 and with incomplete injuries.

Patho-anatomy/physiology

The major underlying abnormality in SCI-related OH is due to sympathetic interruption. The lack of sympathetically mediated reflex vasoconstriction, especially in large vascular beds, such as those supplying the splanchnic region and skeletal muscle result in an inability to compensate for changes in posture.3,5 The gravitational effect of venous pooling in the lower extremities is accompanied by a lack of compensatory changes in other vascular beds, leading to a fall in blood pressure. Venous pooling results in reduced filling pressure at the heart, and a decrease in the end-diastolic filling volume and stroke volume. Tachycardia may occur due to reflex vagal inhibition but is not sufficient to compensate for the reduced sympathetic response.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

OH subsequent to SCI often, but not always, improves over time.2,3,5 Compensatory changes in other vascular beds may contribute to blood pressure homeostasis. Reduced blood flow to the kidneys may activate afferent glomerular dilatation and result in the stimulation of the renin-angiotensin aldosterone system. Other potential mechanisms for improvement over time include vascular wall receptor hypersensitivity, some recovery of postural reflexes at the spinal level, and increased skeletal muscle tone. Tolerance to symptoms of OH often develops over time even with continued evidence of postural reduction in blood pressure in the upright position. It has been suggested that autoregulation of cerebral blood flow, rather than systemic blood pressure, may play a dominant role in the adaptation to OH.6 In the acute stage, OH is a result of losing vasomotor tone coupled with venous pooling in the peripheral and splanchnic vasculature. In the chronic stage, OH is due to the reduction/loss of sympathetic activity below the level of the injury. Muscle atrophy below the level of the lesion also contributes to venous pooling in the lower extremities.7

Specific secondary or associated conditions and complications

Postural hypotension may be influenced by several factors, many of which are reversible.2,3 These include rapid changes in position and prolonged recumbency. Hypotension may be worse in the morning on rising. Heavy meals may exacerbate a fall in blood pressure (and contribute postprandial hypotension) in response to shunting of blood to the splanchnic circulation after a meal.4,8 Physical exertion, alcohol intake, or a hot environment can precipitate hypotension by promoting vasodilatation. Sepsis and dehydration can worsen symptoms. Several medications can induce or worsen OH, including the following common medications: tricyclic antidepressants, antihypertensives, diuretics, narcotic analgesics, alpha-1 antagonists such as tamsulosin, and some muscle relaxants like tizanidine.4 Deconditioning after prolonged bedrest exacerbates OH, which is especially clinically relevant in the acute phase after SCI. The late development or worsening of OH months or years after injury may be a sign of posttraumatic syringomyelia.

Essentials of Assessment

History

Many of the symptoms of OH occur as a result of cerebral hypoperfusion.9 These include dizziness, light-headedness, loss of consciousness, impaired concentration, and visual disturbances such as blurred vision, scotoma, tunnel vision, or color defects. Pallor or auditory deficits may also occur. Sometimes symptoms may be nonspecific, for example generalized weakness, lethargy, or nausea. A suboccipital/paracervical headache (aka “coat hanger headache”) may be a manifestation of hypoperfusion of continuously active paracervical muscles. Excess sweating may occur above the level of injury. The presence of secondary or associated factors mentioned above that could be precipitating or worsening OH should be assessed during history taking.

Physical examination

Blood pressure should be measured when the patient is in the supine position and at least 3 minutes after assuming the upright position.1

Functional assessment

OH may hinder functional assessment and participation in rehabilitation therapies because of the occurrence of symptoms with sitting up or standing. This can result in missed therapy sessions and also play a role in patient safety and falls.

Laboratory studies

Laboratory testing is primarily focused on ruling out non-neurologic causes of OH (e.g., blood loss, dehydration, sepsis, or endocrine disorders) and often includes a complete blood count, electrolyte assessment, and blood glucose level. While not routinely needed, additional testing, such as a morning cortisol level to check for adrenocortical insufficiency, may be indicated if the diagnosis is unclear or if specific disorders are suspected.9  

Imaging

Late occurrence or worsening of OH months or years after SCI should prompt suspicion of posttraumatic syringomyelia, and appropriate diagnostic imaging such as spinal magnetic resonance imaging (MRI) is indicated.

Supplemental assessment tools

Autonomic testing may be done in specialized centers,9 but its role in SCI-related neurogenic OH is not established. Examples include testing heart rate variability with deep breathing and during Valsalva maneuver, and a head-up tilt table test as a tool for evaluation of orthostatic stress. Depending on timing of symptoms, it may be helpful to perform BP measurements following exercise or meals.

Early predictions of outcomes

Frequency and severity of symptoms, time upright before onset of symptoms, influence on activities of daily living, and blood pressure can provide an indication of the severity of OH or response to treatment.10 Those with incomplete or thoracic injuries are more likely to resolve rapidly, though symptoms improve in most cases irrespective of level and completeness of injury.

Social role and social support system

Severe, protracted OH can limit time in a wheelchair and curtail community participation with a negative impact on quality of life.

Professional issues

Reassurance about the typical time course of SCI-related OH with improvement in symptoms after the acute phase is helpful to patients and caregivers who are struggling with OH.

Rehabilitation Management and Treatments

At different disease stages

No single treatment for OH in SCI is consistently effective. Success may be increased by combining and individualizing management.3,9,10 The goal of treatment is to alleviate the disability caused by symptoms, rather than to achieve a specific minimum blood pressure measurement.

A number of practical nonpharmacologic measures can be taken to minimize the hypotensive effects, although evidence of effectiveness in SCI is limited for some.3,9 Small, frequent meals may minimize postprandial symptoms. Decreasing alcohol intake can limit resultant vasodilatory effects. Patients may have greater functional capacity before a meal than in the hour following it and may be able to adjust their activities accordingly. If blood pressure is higher later in the day, physical exertion, such as exercise programs or physical therapy, may be better tolerated in the afternoon rather than the early morning. The nocturnal diuresis that sometimes occurs in SCI can lead to inadequate blood volume. Elevating the head of the bed by 5-10 (reverse Trendelenburg position) may reduce nocturnal diuresis, morning postural hypotension, hypovolemia, and supine hypertension, although patients may not be able to tolerate more than a few degrees of head-up tilt during the night. Rapid changes in position should be avoided, as should excessive exertion in hot environments. A review of patient medications is essential, and modification may be indicated to minimize hypotensive side effects. Administering vasoactive medications with meals may be particularly disabling. Liberalizing salt and water intake may improve blood volume, although the benefit of salt loading has not been sufficiently proven in people with SCI and would likely affect neurogenic bladder and bowel management. Abdominal binders and compressive stockings may be used in an attempt to reduce venous pooling through decreased capacitance of leg and abdominal vascular beds. However, donning these may present practical problems for people with SCI and there is conflicting evidence of effectiveness. Repeated and gradual increase in postural challenges, such as with the use of a tilt-table, may be useful in the acute stages. A tilt-in-space or reclining wheelchair is beneficial for accommodating a progressive increase in the sitting angle and also allows reclining in response to symptoms.

Evidence for use of body weight-supported treadmill training to improve orthostatic tolerance is currently insufficient. There is some evidence to support using functional electrical stimulation (FES) in the treatment of OH in SCI.3 FES-induced contraction of leg muscles may increase venous return, cardiac output, and stroke volume that can increase blood pressure and decrease hypotension-related symptoms, and the response appears to be dose dependent and independent of the site of stimulation. However, the time needed for sessions during inpatient rehabilitation seems to limit feasibility in the subacute post-injury period.11 Biofeedback also has some supporting evidence as an intervention for OH in SCI, but clinical usefulness has yet to be proven.12

Pharmacologic management

Several medications have been used to treat OH, though effectiveness varies.9 Pharmacotherapies used for this indication can be divided into two broad categories: fluid expanders that increase the effective circulating blood volume and medications that work to increase peripheral vascular resistance.13 The medications used most frequently in the clinical setting for SCI-related OH include fludrocortisone and midodrine (Table 1).3,14 Only midodrine and droxidopa are currently approved by the Food and Drug Administration (FDA) for the treatment of neurogenic OH. 10,14 Previous evidence suggested that acute doses of atomoxetine might have been efficacious in treating neurogenic OH, although more recent clinical trial results indicated that it was not superior to placebo to ameliorate symptoms.15 Yohimbine has historically been used as a stimulant to treat erectile dysfunction, but has shown some experimental evidence for treatment of neurogenic OH,16 however, data tested within an SCI patient population is lacking.

Table 1. Pharmacological Agents used in the Treatment of OH in SCI 13,17,18

MedicationMechanismDoseDose Adjustment
Commonly used in SCI
    MidodrineaIncreases arteriolar and venous tone via vasoconstriction, increasing standing, sitting, and supine systolic/diastolic blood pressure  10 mg PO TID during daylight hoursUse with caution in patients with renal impairment. Recommend starting dose is 2.5 mg
    FludrocortisoneExpanding intravascular volume through increasing sodium reabsorption from the distal tubules, enhances the sensitivity of α-adrenoreceptors0.1 mg PO daily. Can be uptitrated per week as needed to 0.3 mg daily    N/A
Potentially useful, though experience in SCI is limited
    DroxidopaaSynthetic amino acid analog metabolized directly to norepinephrine by dopa decarboxylase inducing peripheral arterial and venous vasoconstriction100 mg PO TID. Can be uptitrated every 24-48 hours as needed to max dose of 1800 mg daily    N/A
      Atomoxetine  Selectively inhibits the reuptake of norepinephrine with little to no activity at the other neuronal reuptake pumps or receptor      18 mg PO dailyModerate hepatic impairment (Child-Pugh class B): doses should be reduced to 50%. Severe hepatic impairment (Child-Pugh class C): doses should be reduced to 25%
  PyridostigminePrevents the metabolism of acetylcholine and increase tone via action on the nicotinic receptor  60 mg PO TIDLower initial doses may be required in patients with renal impairment
    OctreotideMimics natural somatostatin by inhibiting serotonin release and the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide    12.5-25 micrograms PO daily    N/A
      YohimbineSelectively blocks pre- and post-synaptic a2-adrenergic receptors resulting in increased sympathetic output and increased serum epinephrine and norepinephrine     5.4mg PO TID (notably, recommendation is for treatment of erectile dysfunction and not OH)Dose-dependent transient moderate increase in blood pressure without affecting heart rate. Avoid in patients with pre-existing hypertension and history of psychiatric disorders given its potential to exacerbate anxiety and agitation.

a Only midodrine and droxidopa are FDA-approved for the indication of neurogenic orthostatic hypotension.9

Coordination of care

Activities requiring exertion in the upright position should not be scheduled first thing in the morning when orthostatic tolerance is lowest or right after meals; therefore, a therapy schedule may need to be adjusted accordingly.

Patient & family education

Counseling about avoidance of exacerbating factors and measures that patients and caregivers can take is helpful. For example, patients should be advised to move from a supine to upright position gradually, especially in the morning and to avoid exertion in hot weather. It can be helpful to remind patients to wait at least 30 seconds after sitting up to assume upright positioning.

Emerging/unique interventions

The goal of treatment is to alleviate the disability caused by symptoms, rather than to achieve an optimal target blood pressure reading. Ensuring patient safety should continue to be a priority while optimizing the patient so that they can carry out the prescribed therapy.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Patients with coexisting OH and supine hypertension are especially challenging to manage and require careful titration and trial of medications.8,11 Short-acting antihypertensive agents at night, for example a nitroglycerin patch, may help control nocturnal hypertension without exacerbating daytime OH. Raising the head end of the bed may also mitigate nocturnal supine hypertension.

Cutting Edge/Emerging and Unique Concepts and Practice

Droxidopa, a synthetic amino acid precursor of epinephrine, already has FDA approval for treating OH, and is being studied for use in SCI-related OH.4,17A study in 2017 in Spain found that droxidopa at 300 mg BID dosing increased BP levels and improved patient symptoms and may be an appropriate option to consider in cases refractory to physical and pharmacologic interventions18 A study with data from a VA Hospital showed that 400 mg dosing of droxidopa did not cause excessive increases in supine BP and was effective at increasing seated BP for up to 3 hours in SCI patients.19 Additional studies are underway to evaluate dosing protocols for droxidopa. The norepinephrine reuptake inhibitor, atomoxetine, is also being studied, with one randomized controlled-trial showing atomoxetine to be more effective than midodrine but is not currently FDA-approved for the treatment of OH.14

Spinal cord epidural stimulation for the treatment of autonomic dysfunction in SCI is another emerging area of research, with the goal of utilizing lumbosacral epidural stimulation to attenuate hypotension.20-22 There have been many studies evaluating the role of epidural spinal cord stimulation on recovery of neurologic functions in SCI.22 Evidence within the literature has demonstrated positive effects of epidural spinal cord stimulation on mean arterial pressure and other markers of cardiovascular stability while concurrently facilitating improvements in motor function. Enhancement of motor function may also provide secondary cardiovascular autonomic control.22 

Transcutaneous spinal cord stimulation (t-SCS) is an additional emerging area of research for potential non-invasive treatment of orthostatic hypotension.23-24 Initial research has revealed that while t-SCS appears to significantly increase blood pressure measurements utilizing tilt-table testing in individuals with SCI and previously documented symptomatic orthostatic hypotension25, these autonomic changes may facilitate pathologic reflexes without improved regulation.24

Further clinical trials of spinal cord stimulation are anticipated to study the safety and efficacy of these interventions, with additional efforts to standardize methodology across future studies for implementation in clinical practice.

Significant associations have been demonstrated between orthostatic hypotension symptom burden and neurocognitive test performance for participants with injuries at T6 above and a history of unstable BP control.26 These findings, which have been in individuals without co-occurring traumatic brain injury, imply cardiovascular dysregulation may play a role in cognitive deficits observed in this patient population.

Gaps in the Evidence-Based Knowledge

Given the lack of consistently effective treatment, current emerging therapies need to be further examined and newer therapies need to be developed. Well-designed controlled studies for current treatments still remain limited.3 Newer medications and interventions show promising initial results though require further extensive studies over the long term.

References

  1. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011;21(2):69-72. doi:10.1007/s10286-011-0119-5
  2. Krassioukov A, Linsenmeyer TA, Beck LA, Elliott S, Gorman P, Kirshblum S, Vogel L, Wecht J, Clay S. Evaluation and Management of Autonomic Dysreflexia and Other Autonomic Dysfunctions: Preventing the Highs and Lows. J Spinal Cord Med. 2021 Jul;44(4):631-683. doi: 10.1080/10790268.2021.1925058. PMID: 34270391; PMCID: PMC8288133.
  3. Krassioukov A, Eng JJ, Warburton DE, Teasell R; Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of the management of orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil. 2009;90(5):876-885. doi:10.1016/j.apmr.2009.01.009
  4. Palma JA, Kaufmann H. Management of Orthostatic Hypotension. Continuum (Minneap Minn). 2020 Feb;26(1):154-177. doi:10.1212/CON.0000000000000816
  5. Teasell RW, Arnold MO, Krassioukov A, et al. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil. 2000;81:506-516. doi:10.1053/mr.2000.3848
  6. Sahota IS, Ravensbergen HR, McGrath MS, Claydon VE. Cerebrovascular responses to orthostatic stress after spinal cord injury. J Neurotrauma. 2012;29(15):2446-2456. doi:10.1089/neu.2012.2379
  7. Philips AA, Krassioukov AV. Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms, Maladaptations, and Management. J Neurotrauma. 2015 Dec 15;32(24):1927-42. doi:10.1089/neu.2015.3903
  8. Shibao C, Gamboa A, Diedrich A, Dossett C, Choi L, Farley G, Biaggioni I. Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure. Hypertension. 2007;50(1):54-61. doi:10.1161/HYPERTENSIONAHA.107.091355
  9. Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358:615-24. doi:10.1056/NEJMcp074189
  10. Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7:451-458. doi:10.1016/S1474-4422(08)70088-7
  11. Moineau B, Brown A, Brisbois L, Zivanovic V, Miyatani M, Kapadia N, Hsieh JTC, Popovic MR. Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury. J Spinal Cord Med. 2019;42(sup1):176-185. doi:10.1080/10790268.2019.1638129
  12. Gillis DJ, Wouda M, Hjeltnes N. Non-pharmacological management of orthostatic hypotension after spinal cord injury: a critical review of the literature. Spinal Cord. 2008;46(10):652-9. doi:10.1038/sc.2008.48
  13. Kulkarni S, Jenkins D, Dhar A, Mir F. Treating Lows: Management of Orthostatic Hypotension. J Cardiovasc Pharmacol. 2024;84(3):303-315. doi:10.1097/FJC.0000000000001597
  14. Hale GM, Valdes J, Brenner M. A review of the Treatment of primary Orthostatic Hypotension. Ann Pharmacother. 2017;51(5):417-428. doi:10.1177/1060028016689264
  15. Kaufmann H. L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008;18 Suppl 1:19-24. doi:10.1007/s10286-007-1002-2
  16. Jabir NR, Firoz CK, Zughaibi TA, Alsaadi MA, Abuzenadah AM, Al-Asmari AI, Alsaieedi A, Ahmed BA, Ramu AK, Tabrez S. A literature perspective on the pharmacological applications of yohimbine. Ann Med. 2022;54(1):2861-2875. doi: 10.1080/07853890.2022.2131330
  17. Mwesigwa N, Millar Vernetti P, Kirabo A, et al. Atomoxetine on neurogenic orthostatic hypotension: a randomized, double-blind, placebo-controlled crossover trial. Clin Auton Res. 2024;34(6):561-569. doi:10.1007/s10286-024-01051-2
  18. Canosa-Hermida E, Mondelo-Garcia C, et al. Refractory orthostatic hypotension in a patient with spinal cord injury: Treatment with droxidopa. J Spinal Cord Med. 2018;41(1):115-118. doi:10.1080/10790268.2016.1274093.
  19. Wecht JM, Rosado-Rivera D, Weir JP, Ivan A, Yen C, Bauman WA. Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury. Arch Phys Med Rehabil. 2013:94(10):2006-12. doi:10.1016/j.apmr.2013.03.028
  20. Sarafis ZK, Monga AK, Phillips AA, Krassioukov AV. Is Technology for Orthostatic Hypotension Ready for Primetime? PM R. 2018;10(9 Suppl 2):S249-S263. doi: 10.1016/j.pmrj.2018.04.011.
  21. Luz A, Rupp R, Ahmadi R, Weidner N. Beyond treatment of chronic pain: a scoping review about epidural electrical spinal cord stimulation to restore sensorimotor and autonomic function after spinal cord injury. Neurol Res Pract. 2023;5(1):14. doi:10.1186/s42466-023-00241-z
  22. Chalif JI, Chavarro VS, Mensah E, et al. Epidural Spinal Cord Stimulation for Spinal Cord Injury in Humans: A Systematic Review. J Clin Med. 2024;13(4):1090. doi:10.3390/jcm13041090
  23. Solinsky R, Burns K, Tuthill C, Hamner JW, Taylor JA. Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury. Am J Physiol Heart Circ Physiol. 2024;326(1):H116-H122. doi:10.1152/ajpheart.00588.2023
  24. Bojanic T, McCaughey EJ, Finn HT, et al. The effect of abdominal functional electrical stimulation on blood pressure in people with high level spinal cord injury. Spinal Cord. 2025;63(1):31-37. doi:10.1038/s41393-024-01046-w
  25. Beliaeva NN, Moshonkina TR, Mamontov OV, et al. Transcutaneous Spinal Cord Stimulation Attenuates Blood Pressure Drops in Orthostasis. Life (Basel). 2022;13(1):26. Published 2022 Dec 22. doi:10.3390/life13010026
  26. Nightingale TE, Zheng MMZ, Sachdeva R, Phillips AA, Krassioukov AV. Diverse cognitive impairment after spinal cord injury is associated with orthostatic hypotension symptom burden. Physiol Behav. 2020;213:112742. doi:10.1016/j.physbeh.2019.112742

Bibliography

Sabharwal S. Orthostatic Hypotension. In: Sabharwal S, ed. Essentials of Spinal Cord Medicine. New York, NY: Demos Publishing; 2014:257-262.

Original Version of the Topic

Sunil Sabharwal, MD. Orthostatic Hypotension in SCI. 7/20/2012

Previous Revision(s) of the Topic

Vincent Huang, MD, Raman Sharma, MD, Sunil Sabharwal, MD. Orthostatic Hypotension in SCI. 11/29/2017

Rafer Willenberg, MD, PhD, Jaimie John, MD, and Sunil Sabharwal, MD. Orthostatic Hypotension in SCI. 5/11/2022

Author Disclosure

Kaitlyn DeHority, MD
Nothing to Disclose

Colette Piasecki-Masters, MD
Nothing to Disclose

Elizabeth Roux, BA
Nothing to Disclose

Sunil Sabharwal, MD
Demos Medical Publishing, Receipt of Royalties, Book author/editor