First published May 2007, updated December 2021

Key points: 

  • Patients with orthostatic hypotension should be fully assessed to determine the underlying cause.
  • Conservative measures may help to alleviate symptoms.
  • Midodrine and/or fludrocortisone are the first line pharmacological treatments.
  • Other agents include erythropoietin, octreotide, desmopressin and NSAIDs.
  • Treatment may be complicated by drug side effects, especially supine hypertension.

Orthostatic (or postural) hypotension is defined as a drop in blood pressure of either 20mmHg systolic or 10mmHg diastolic within three minutes of adopting an upright position from lying down1. It may lead to light-headedness, blackouts and falls, but it can also be asymptomatic, in which case treatment is not warranted. Orthostatic hypotension forms part of a larger group of disorders labelled orthostatic intolerance. This group comprises conditions that only produce symptoms upon standing and includes orthostatic hypotension, postural orthostatic hypotension (POTS — a rise in heart rate of more than 30bpm on standing) and neurocardiogenic syncope (a fall, often delayed, of both blood pressure and heart rate on standing). Orthostatic hypotension becomes increasingly common with age, affecting approximately 20 per cent of elderly patients2. It results in significant morbidity and can be very disabling, even resulting in a chair or bedbound existence.

Pathophysiology

In order to better understand the possible causes and treatments it is necessary to explain the normal mechanisms that enable us to stand. When rising from a supine position approximately 500mls of blood descends, with the help of gravity, to our lower extremities. The decrease in venous return to the heart activates baroreceptors in the carotid arteries and aortic arch, which increase sympathetic tone and inhibit parasympathetic tone. This causes peripheral vasoconstriction and an increase in heart rate to maintain adequate cerebral perfusion. On continued standing, there is activation of the renin-angiotensin system and release of vasopressin to maintain circulating volume. Normal standing, therefore, results in a small drop in blood pressure and a slight rise in the pulse rate.

Causes of orthostatic hypotension

Any condition that disrupts part of this normal response to standing can result in orthostatic intolerance. This includes volume depletion, autonomic dysfunction, venous pooling and failure of the renin-angiotensin system (Table 1). Volume depletion is possibly the most common cause of orthostatic hypotension, and can be either acute or chronic. Acute causes include dehydration and haemorrhage. Chronic causes include medications (such as diuretics), adrenal insufficiency and salt losing nephropathy. It is also possible to get relative fluid depletion due to peripheral vasodilatation. Autonomic dysfunction is usually part of a larger disease process such as diabetes, polyneuropathy or amyloid, or it can be secondary to drugs and toxins. If a patient has autonomic dysfunction with no clear cause it is termed primary chronic autoimmune failure. This is further divided into three classes. If autonomic failure is the sole feature it is termed pure autonomic failure, or Bradbury-Egglestone syndrome. If autonomic dysfunction occurs in combination with central neurodegeneration (parkinsonism and cerebellar ataxia) it is termed multisystem atrophy. The third form is when autonomic failure occurs in conjunction with Parkinson’s disease3. Cardiovascular disease can also cause orthostatic hypotension. Causes include myocardial infarction, congestive cardiac failure, constrictive pericarditis and aortic stenosis.

Table 1. Common causes of orthostatic hypotension

Volume depletion

·       Dehydration

·       Burns

·       Haemorrhage

·       Medications — diuretics, alpha-blockers, nitrates

·       Adrenal insufficiency

·       Uncontrolled diabetes mellitus

·       Diabetes insipidus

·       Salt-losing nephropathy

Automatic dysfunction

·       Primary autonomic failure

·       Pure autonomic failure (Bradbury-Egglestone syndrome)

·       Multi-system atrophy

·       Parkinson’s disease

·       Part of a disease process

·       Diabetes mellitus

·       Amyloid B12 or folate deficiency

·       Stroke

·       Sarcoid

·       Polyneuropathy

·       Toxins

·       Medications — levodopa, tricyclic antidepressants, tranquillisers

Cardiovascular

·       Aortic stenosis

·        Congestive cardiac failure

·       Arrythmias

·       Myocarditis

·       Pericarditis

Venous Pooling

·       Sepsis

·       Fever

·       Alcohol

·       Varicose Veins

·       AV malformations

·       Prolonged bed rest

Assessment

Patients with orthostatic hypotension may present with light-headedness, blurred vision, fatigue, falls, blackouts or even seizures. Symptoms that occur soon after standing may point to the diagnosis, but there may be a long delay of up to 45 minutes between standing and syncopal symptoms. The history and examination need to concentrate on confirming the diagnosis and elucidating a cause, if possible. Firstly, the diagnosis is confirmed by measuring the postural blood pressure. The patient is positioned in the supine position for five minutes and then the blood pressure and pulse is taken. The patient is then asked to stand and both measurements are repeated at one and three minutes. A drop in blood pressure of more than 20/10mmHg would confirm orthostatic hypotension. A pulse increase of more than 20bpm would suggest volume depletion, whereas a pulse increase of less than 10bpm would suggest autonomic dysfunction.

Patients may not demonstrate a postural drop in blood pressure at clinic, even if orthostatic hypotension is strongly suspected from the history. There are several possible explanations for this. Orthostatic hypotension is often worse in the morning after a night lying down for sleep and may not be detected if looked for later in the day. Also, symptoms and signs can vary from day to day, depending on the patient’s fluid status and autonomic tone. Alternatively, patients may have a delayed postural drop, occurring up to 45 minutes after standing. If the symptoms are suggestive of orthostatic hypotension, but a postural drop is not demonstrable in clinic, it may be necessary to confirm the diagnosis with a head-up tilt-table test.

To look for possible causes, the history should cover cardiovascular, neurological and endocrine systems. It is important to ask about associated symptoms that may suggest autonomic dysfunction, such as incontinence, gastroparesis, impotence, blurred vision, decreased sweating and constipation. A comprehensive drug and alcohol history also needs to be undertaken. The examination should include assessment of the patient’s volume status, auscultation for carotid bruits and heart murmurs — and also examination for signs of parkinsonism, peripheral neuropathy or stroke.

Investigations

Depending on the results of the initial assessment some of the following investigations may need to be performed:

  • full blood count for anaemia;
  • urea and electrolytes – dehydration, adrenal insufficiency, diabetes insipidus;
  • glucose — diabetes; > B12;
  • synacthen test — adrenal insufficiency;
  • measurement of plasma norepinephrine levels in supine and upright position. In autonomic failure the supine levels will be low with no dramatic increase on standing. Other causes will demonstrate a rise in standing norepinephrine levels;
  • electrocardiogram; and
  • head-up tilt test.

Head-up tilt-table testing

Head-up tilt-table testing allows assessment of postural blood pressure and pulse if the diagnosis is in doubt or the patient has difficulty standing independently. Protocols for head-up tilt tests vary between institutions. The patient is initially positioned in the supine position, with heart rate and blood pressure monitoring. The bed is then tilted head-up to around 60–80 degrees. The patient is kept in this position for 30–45 minutes with continued heart rate and blood pressure monitoring. A drop in blood pressure of more than 20/10mmHg, with either no change or a possible increase in heart rate, confirms a diagnosis of orthostatic hypotension. A drop in both heart rate and blood pressure would suggest neurocardiogenic syncope. A pulse rate rise of over 30bpm, or to more than 120bpm, with only a slight drop in blood pressure

Management

There are several treatment options available for orthostatic hypotension, which can be broadly grouped into conservative and pharmacological. If there is a cause underlying the orthostatic symptoms, such as vitamin B12 deficiency, then this needs to be treated. If current medications are the causative factor, then thought needs to be given to stopping them or switching over to an alternative.

Conservative measures

Conservative measures to treat orthostatic hypotension include:

  • avoid standing up too quickly;
  • maintain, or even increase, salt and water intake;
  • eat small frequent meals to avoid post-prandial hypotension;
  • avoid agents that lead to volume depletion, such as alcohol and diuretics;
  • tilt the head of the bed up at night to 20 degrees;
  • wear waist-length compression stockings; and
  • drink coffee (caffeine acts as a vasopressor and so may, in theory, alleviate symptoms).

Thought also needs to be given to preventing injuries in vulnerable elderly people. Osteoporosis treatment and hip protectors should be considered.

Drug treatment

Several pharmacological therapies have been tried to alleviate orthostatic hypotension, although convincing evidence of efficacy is lacking in many of them. The two most widely used agents in the UK are fludrocortisone and midodrine, although the latter is not licenced and so is only available on a named-patient basis.

Midodrine is a precursor of desglymidodrine, an alpha-1 agonist. It causes both veno and arterioconstriction, increasing peripheral resistance. It is given at a dose of 2.5mg to 10mg three times daily. In a randomised controlled trial, the mean increase in standing blood pressure was about 20mmHg systolic with a dose of 10mg three times daily5. However, despite this increase in blood pressure, there was only a modest decrease in patients’ symptoms. Side effects of midodrine include urinary retention and supine hypertension, which occurs in 25 per cent of patients. Fludrocortisone is a mineralocorticoid that increases salt and water retention, resulting in increased circulating volume. It is given at a dose of 100– 1000mcg/day and can take one to two weeks to work. Side effects include hypokalaemia, supine hypertension and oedema, but it is usually well tolerated2 . Ephedrine, another sympathomimetic, is also used to treat orthostatic hypotension. However, it appears less effective than midodrine2. Continuous ambulatory norepinephrine infusion has been used in refractory cases of orthostatic hypotension6.

Around 25 per cent of patients with chronic orthostatic hypotension have a normocytic anaemia. Treatment with erythropoietin in some of these patients has resulted in improvement of their orthostatic hypotension7. Other therapies that have been used with some success include octreotide — alone or in combination with midodrine8, desmopressin9 , non-steroidal anti-inflammatories (NSAIDs)2, pindolol10, clonidine and SSRIs4. It may be necessary to use these agents in combination to achieve adequate control of the blood pressure and symptoms. However, management may be problematic as both fludrocortisone and midodrine can cause supine hypertension. This is an increase in a patient’s supine blood pressure, which if sustained at levels of more than 180/100mmHg, can result in left ventricular hypertrophy, nocturnal diuresis and worsening of orthostatic symptoms. The treatment is to avoid giving pressor agents, such as midodrine, in the evening and to tilt the head of the bed up at night. However, it can be difficult to manage and requires balancing the hypertension risk against a patient’s orthostatic symptoms.

Conclusion

Orthostatic hypotension is a common problem in the elderly with a large number of possible causes. It requires a thorough assessment and evaluation. There are many potential therapies available to try and alleviate symptoms, but unfortunately it can prove to be a difficult problem to manage.

Conflict of interest: none declared.

References

  1. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Neurology 1996; 46: 1470
  2. Frischman WH, Azer V, Sica D. Drug treatment of orthostatic hypotension and vasovagal syncope. Heart Disease 2003; 5: 49–64
  3. Goldstein DS, Robertson D, Esler M et al. Dysautonomias: clinical disorders of the autonomic nervous system. Ann of Int Med; 137(9): 753–64
  4. Sealey B. Diagnosis and management of vasovagal syncope and dysautonomia. AACN Clinical issues; 15(3): 462–77
  5. Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. JAMA 1997; 277(13): 1046–51
  6. Oldenberg O, Mitchell A, Nurnberger J et al. Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension. J Am Coll Cardiol 2001; 37: 219–223
  7. Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. New Engl J Med 1993; 329: 611–15
  8. Hoeldtke RD, Hovarth GG, Bryner KD, Hobbs GR. Treatment of orthostatic hypotension with midodrine and octreotide. J Clin Endo and Met; 83(2): 339–43
  9. 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. BMJ 1986; 293: 353–54
  10. Man in ‘t Veld JD, Schalekamp MADH. Pindolol acts as betaadrenoceptor agonist in orthostatic hypotension: therapeutic implications. BMJ 1981; 282: 929–931