- Orthostatic hypotension is defined as a significant drop in blood pressure upon standing and can be caused by autonomic failure, volume depletion, medications, and aging.
- It is more common in elderly patients due to impaired baroreceptor sensitivity. Symptoms include dizziness, weakness, and fainting.
- Treatment involves non-pharmacological measures like lifestyle modifications, increasing salt/water intake, and compression stockings. Pharmacotherapy includes fludrocortisone and midodrine to ameliorate symptoms.
3. Definition
What is Orthostatic Hypotension?
• The significant reduction in blood
pressure upon standing (1).
1. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated
syncope and the postural tachycardia syndrome. Clin Auton Res 2011; 21:69.
4. EPIDEMIOLOGY
• Orthostatic hypotension is more common in the elderly due,
at least in part to impaired baroreceptors sensitivity(1,2).
• Epidemiologic surveys have found postural hypotension in
20 percent of patients over 65 years old (3,4).
1. Shibao C, Grijalva CG, Raj SR, et al. Orthostatic hypotension-related hospitalizations in the United States. Am J Med 2007; 120:975.
2 Finucane C, O'Connell MD, Fan CW, et al. Age-related normative changes in phasic orthostatic blood pressure in a large population study: findings from The Irish Longitudinal
Study on Ageing (TILDA). Circulation 2014; 130:1780.
3 Rutan GH, Hermanson B, Bild DE, et al. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 1992; 19:508.
4 Valbusa F, Labat C, Salvi P, et al. Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. J Hypertens 2012; 30:53.
8. ETIOLOGIES
• Many disorders can cause
postural hypotension, with the
two major mechanisms being:
• Autonomic failure/NOH Neurogenic
orthostatic hypotension (which can be
caused by multiple disorders)
• Volume depletion (1,2)
• Medications
• Aging
1. Kaufmann H. Neurally mediated syncope and syncope due to autonomic failure: differences and similarities. J
Clin Neurophysiol 1997; 14:183.
2. Téllez MJ, Norcliffe-Kaufmann LJ, Lenina S, et al. Usefulness of tilt-induced heart rate changes in the differential
diagnosis of vasovagal syncope and chronic autonomic failure. Clin Auton Res 2009; 19:375.
9. Autonomic Failure (NOH)
• Disorder where sympathetic neurons do not release
norepinephrine appropriately resulting in an impaired
vasoconstriction (1).
• Neurodegenerative diseases
• Parkinson disease
• Dementia with Lewy bodies
• Multiple system atrophy
• Pure autonomic failure (Bradbury-Eggleston syndrome
• Neuropathies
• Diabetes is the most common cause
1. Metzler M, Duerr S, Granata R, et al. Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management. J Neurol 2013; 260:2212
10. Volume depletion
• Acute or subacute volume depletion due to:
• Diuretics
• Hyperglycemia
• Hemorrhage
• Diarrhea or vomiting
11. Medications
• Orthostatic hypotension is a common side effect of
medications through a variety of mechanisms, including
peripheral vasodilation, autonomic dysfunction and volume
depletion (1)
1. Perlmuter LC, Sarda G, Casavant V, Mosnaim AD. A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension. Am J Ther 2013; 20:279.
12. Examples of drugs that can cause or exacerbate
orthostatic hypotension(1)
• Alcohol
• Alpha blockers: Terazosin (eg)
• Antidepressant drugs: SSRIs,
trazodone, MAO inhibitors, tricyclic
antidepressants
• Antihypertensive drugs: Sympathetic
blockers (eg)
• Antiparkinsonism drugs: Levodopa,
pramipexole, ropinirole (egs)
• Antipsychotic drugs: Olanzapine,
risperidone (egs)
• Beta-blocker drugs: Propranolol (eg)
• Diuretic drugs: Hydrochlorothiazide,
furosemide (egs)
• Muscle relaxant: Tizanidine (eg)
Narcotic analgesic drugs: Morphine
(eg)
• Phosphodiesterase inhibitors:
Sildenafil, tadalafil (egs)
• Sedatives/hypnotic : Temazepam (eg)
• Vasodilator: Hydralazine, nitroglycerin,
calcium channel blockers (eg)
1. Perlmuter LC, Sarda G, Casavant V, Mosnaim AD. A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension. Am J Ther 2013; 20:279.
13. Aging
• In addition to the autonomic disorders, a decrease in
baroreceptors sensitivity is assumed to be involved in the
frequent form of postural hypotension seen in elderly
patients (1).
1. Tonkin AL, Wing LM. Effects of age and isolated systolic hypertension on cardiovascular reflexes. J Hypertens 1994; 12:1083
14. SYPMTOMS • Symptoms result from cerebral
hypoperfusion
• Generalized weakness
• Dizziness or lightheadedness
• Visual blurring or darkening of the visual
fields
• In severe cases: loss of consciousness
(syncope)
• Other symptoms: Fatigue, cognitive slowing.
• Neck pain and headache localized in the
suboccipital posterior cervical, and shoulder
region (the coat-hanger headache) are
reported in 50 to 90% of patients (1).
1. Zanasi A, Tincani E, Evandri V, et al. Meal-induced blood pressure variation and cardiovascular mortality in
ambulatory hypertensive elderly patients: preliminary results. J Hypertens 2012; 30:2125.
15. DIAGNOSIS
• Postural hypotension is
diagnosed when within two to
five minutes of quiet standing
(after a 5 minute period of
supine rest), one or both of the
following is present (1).
1.At least 20 mmHg fall in
systolic pressure
2.At least a 10 mmHg fall in
diastolic pressure.
1. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic
hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res
2011; 21:69.
16. EVALUATION
• Diagnostic evaluation to identify treatable conditions that may
be causative or contributor to orthostatic hypotension(1).
Detailed medication list
Recent medical history of potential volume loss (vomiting, diarrhea, fluid
restriction, fever)
Medical history of CHF, malignancy, DM, alcoholism
Evidence of neurologic history and examination of parkinsonism, ataxia,
peripheral neuropathy or dysautonomia (eg, abnormal pupillary response, hx of
constipation or erectile dysfunction)
1. Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007; 120:841.
17. COMPLICATIONS
• According to several population-based studies, orthostatic
hypotension is a risk factor for cardiovascular and all-cause
mortality, usually due to underlying causes and associated
diseases.
• Orthostatic hypotension can cause falling, which has
significant associated morbidity, particularly in a frail elderly
population (1,2).
1.van Hateren KJ, Kleefstra N, Blanker MH, et al. Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study. Br J Gen Pract 2012; 62:e696.
2.Gangavati A, Hajjar I, Quach L, et al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living,
intellect, and zest in the elderly of Boston study. J Am Geriatr Soc 2011; 59:383.
18. TREATMENT
• Treatment goals
• In general treatment is titrated to symptoms relief rather
than correction of measured orthostatic hypotension.
• Asymptomatic orthostatic hypotension is common and of
uncertain clinical relevance (1).
• Nonpharmacologic measures
• Pharmacotherapy
1.van Hateren KJ, Kleefstra N, Blanker MH, et al. Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study. Br J Gen Pract 2012; 62:e696
19. Nonpharmacologic measures
• Directed toward the patient with chronic orthostatic hypotension due
to autonomic dysfunction, clinical experience suggests benefit while
avoiding medication side effects (1).
• The patient with acute orthostatic hypotension due to volume
depletion should be treated with volume replacement
• Removal of offending medications: removal of drugs that cause
orthostatic hypotension is the first management step
1.Gangavati A, Hajjar I, Quach L, et al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance,
independent living, intellect, and zest in the elderly of Boston study. J Am Geriatr Soc 2011; 59:383.
20. Nonpharmacologic measures
• Lifestyle modifications
Arising slowly, in stages, from supine to seated to standing
Avoid straining, coughing, and walking in hot weather; this activities reduce
venous return and worsen orthostatic hypotension
Maintain hydration and avoiding over-heating
Raising the head of the bed 10 to 20 degrees decreases the renal perfusion,
activating the renin-angiotensin-aldosterone system and decreasing nocturnal
diuresis
The use of custom-fitted elastic stockings to minimize the peripheral blood
pooling. It is essential that such stocking extend to the waist, since most
peripheral pooling occurs in the splanchnic circulation(1)
1. Raj SR, Coffin ST. Medical therapy and physical maneuvers in the treatment of the vasovagal syncope and orthostatic hypotension. Prog Cardiovasc Dis 2013; 55:425.
21. Nonpharmacologic measures
• Increase salt and water intake (1,2,3)
• Modification of meals
• Avoiding large meals
• Ingesting meals low in carbohydrate
• Minimizing alcohol intake
• Drinking water with meals (the effect of water is grater in the hour after
ingestion)
• Avoiding activities or sudden standing immediately after eating
1.Shannon JR, Diedrich A, Biaggioni I, et al. Water drinking as a treatment for orthostatic syndromes. Am J Med 2002; 112:355.
2.Young TM, Mathias CJ. The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure. J Neurol
Neurosurg Psychiatry 2004; 75:1737.
3.Humm AM, Mason LM, Mathias CJ. Effects of water drinking on cardiovascular responses to supine exercise and on orthostatic hypotension after exercise in pure autonomic failure. J Neurol
Neurosurg Psychiatry 2008; 79:1160.
22. Pharmacotherapy
• Numerous agents have been utilized, but there is limited evidence to
support the use of any of these agents (1,2)
• The goal is to ameliorate symptoms while avoiding side effects. It is
important to analyze symptoms rather than BP values
Fludrocortisone, a synthetic mineralocorticoid is the medication of first choice. It
increases the blood volume
Sympathomimetic agents
Midodrine, a peripheral selective alpha-1-adrenergic agonist
1.Logan IC, Witham MD. Efficacy of treatments for orthostatic hypotension: a systematic review. Age Ageing 2012; 41:587.
2.Schoffer KL, Henderson RD, O'Maley K, O'Sullivan JD. Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. Mov Disord
2007; 22:1543.
23. Pharmacotherapy
• Supplementary agents
• May be used in combination therapy with first or second line agents in
patients with persistent symptoms
• Pyridostigmine (1)
• NSAIDs (2)
• Caffeine (3)
• Erythropoietin (4)
1.Singer W, Sandroni P, Opfer-Gehrking TL, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 2006; 63:513.
2. Kochar MS, Itskovitz HD. Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin. Lancet 1978; 1:1011.
3. Onrot J, Goldberg MR, Biaggioni I, et al. Hemodynamic and humoral effects of caffeine in autonomic failure. Therapeutic implications for postprandial hypotension. N Engl J Med 1985;
313:549
4. Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. N Engl J Med 1993; 329:611.
24. Pharmacotherapy
• Third line and experimental agents
• Vasopressin analogues (1)
• Yohimbine (2)
• Somatostatin (3)
• Dihydroergotamine (4)
• Ergotamine/caffeine (5)
• Atomexitine (6)
1. Mathias CJ, Fosbraey P, da Costa DF, et al. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Br Med J (Clin Res Ed) 1986; 293:353.
2. Onrot J, Goldberg MR, Biaggioni I, et al. Oral yohimbine in human autonomic failure. Neurology 1987; 37:215.
3. Hoeldtke RD, Israel BC. Treatment of orthostatic hypotension with octreotide. J Clin Endocrinol Metab 1989; 68:1051.
4. Jennings G, Esler M, Holmes R. Treatment of orthostatic hypotension with dihydroergotamine. Br Med J 1979; 2:307.
5. Nwazue VC, Raj SR. Confounders of vasovagal syncope: orthostatic hypotension. Cardiol Clin 2013; 31:89.
6. Ramirez CE, Okamoto LE, Arnold AC, et al. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 2014; 64:1235.
