Guideline on Management of Orthostatic (Postural) Hypotension

• Definition
• Prevelence
• Consequences of Orthostatic Hypotension
• Conditions causing Orthostatic Hypotension
• Symptoms of Orthostatic Hypotension
• Presentation and Assessment
• Flow Chart Summary of Diagnosis and Treatment of Orthostatic Hypotension
• Investigations
• Treatment
• Pharmacological Treatment

Definition

Orthostatic hypotension (OH) is an abnormal drop in blood pressure (BP) on standing¹ and is defined as a fall in blood pressure (BP) of at least 20 mm Hg systolic and/or 10 mm Hg diastolic BP within three minutes in the upright position² or a drop in systolic BP below 90mm Hg.

It is important to ask patients if they have symptoms on standing such as dizziness/ light-headedness. Asymptomatic orthostatic hypotension may not need to be treated in cognitively intact individuals. Cognitively impaired individuals may not report classic symptoms and may become intermittently drowsy or fall without warning.

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Prevalence

The prevalence of OH increases with age. In the USA, OH is found in <5% of people aged 45-49 years old, approximately 15% in those aged 65-69 and over 25% of those aged > 85 years old. Prevalence of OH was 14-20% in community, 15-25% in primary care and 31% in care home cohorts in one systematic review and meta-analysis.⁵ OH is common in older inpatients¹ and is seen in almost a quarter (24%) of emergency department presentations with syncope, a fifth (19%) of older trauma inpatients and 68% of older general medicine inpatients.²

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Consequences of Orthostatic Hypotension

OH worsens physical function and impairs balance and ability to perform activities of daily living. OH increases the risk of falls, fractures, heart failure, coronary heart disease, stroke, atrial fibrillation, road-traffic accidents and all-cause mortality.^1,2 Some studies suggest that OH also increases the risk of cognitive impairment, dementia, and depression. It is unclear if risk differs between symptomatic and asymptomatic patients and between age groups.¹

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Conditions causing Orthostatic Hypotension^1,2

*SSRIs- selective serotonin reuptake inhibitors     ** TCAs- tricyclic antidepressants

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Symptoms of Orthostatic Hypotension^1,2

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Presentation and Assessment

Symptoms (see table) are triggered by changes in posture and usually resolve on lying down or sitting. Symptoms may occur when the person gets up from bed or throughout the day as they change position e.g. from sitting to standing. If symptoms occur in relation to changes in posture, a check for postural hypotension should be done.¹

The nature of symptoms, onset in relation to changes in posture and if they are recurrent or isolated should be explored. Symptoms can be affected by diurnal variability, food intake, hydration, ambient temperature, immobility and deconditioning.^1,2 Medication history is important especially if symptoms have occurred after medicine initiation or dose changes. Seek to identify the cause which may be multifactorial and tailor clinical examination to identify features related to the symptoms and probable causes. For example a patient who describes slowness of movement and tremor may have rigidity suggestive of Parkinson’s.¹

Cardiovascular medicines
Angiotensin-converting enzyme inhibitors, for example ramipril
Angiotensin II inhibitors, for example candesartan cilexetil, losartan
Alpha blockers, for example doxazosin, tamsulosin hydrochloride
Beta blockers, for example bisoprolol fumarate
Calcium channel blockers, for example amlodipine
Centrally acting antihypertensives, for example moxonidine, clonidine hydrochloride
Diuretics, for example furosemide, bendroflumethiazide
Vasodilators, for example nitrates such as isosorbide mononitrate

Psychotropic medicines
Anti-Parkinson medicines, for example levodopa, ropinirole
Antipsychotics, for example chlorpromazine hydrochloride, quetiapine
Selective serotonin reuptake inhibitors, for example citalopram, fluoxetine
Serotonin and noradrenaline reuptake inhibitors, for example venlafaxine, duloxetine
Monoamine oxidase inhibitors, for example phenelzine, selegiline hydrochloride
Prochlorperazine
Tricyclic antidepressants, for example amitriptyline hydrochloride

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Flow Chart Summary of Diagnosis and Treatment of Orthostatic Hypotension

* How to measure lying and standing BP https://www.rcplondon.ac.uk/projects/outputs/measurement-lying-and-standing-blood-pressure-brief-guide-clinical-staff
** Specialist advice can be obtained from cardiology, general medicine, neurology, renal or older people’s medicine dependent on patient co-morbidities if required

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Investigations

Checking lying and standing blood pressure (BP) involves measuring BP lying down, on standing and then after standing for three minutes.² Information on how to measure lying and standing blood pressure can be found at https://www.rcplondon.ac.uk/projects/outputs/measurement-lying-and-standing-blood-pressure-brief-guide-clinical-staff

Measurement of BP after three minutes may be required if a patient reports symptoms after this time. Otherwise, delayed OH may be missed.^1,2

Lying and standing BP can be checked alongside heart rate on automated devices. This method will clearly show what happens to BP in the erect posture.2 If OH is found with an increase in heart rate of <15 beats per minute, this may suggest a neurogenic cause and an increase in heart rate of > 15 beats per minute may suggest a non-neurogenic cause. This may not be accurate if the patient is taking beta-blockers or other medicines that cause bradycardia.1
Some patients have no symptoms and OH is detected incidentally. The clinical significance of asymptomatic OH is not established.1 Tilt-table testing is rarely required and should only be requested after specialist advice.

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Treatment

Non-pharmacological Treatment and Lifestyle Advice^1,2,6

Patients who have reproducible warning signs of OH should be advised to sit or lie down immediately on experiencing symptoms.

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Pharmacological Treatment

Medicines to treat OH are usually started by, or under the advice of, a specialist if symptoms are not controlled by non-pharmacological measures e.g. specialist in general medicine, neurology, older people’s or renal medicine. However, treatment can be started in Primary Care. Treatment of OH should be continued, modified and monitored in Primary Care. The usual treatments are fludrocortisone or midodrine. The use of fludrocortisone in OH is an unlicensed indication whilst midodrine is only indicated for postural hypotension due to autonomic dysfunction.
Evidence for fludrocortisone and midodrine is weak and mainly drawn from small randomised controlled trials with short-term follow up.1

Fludrocortisone tablets (100 micrograms)

Unlicensed indication, recommended in BNF for neuropathic postural hypotension

Dose: Initially 50 to 100 micrograms once daily, increased if symptoms remain poorly controlled by no more than 100micrograms/ week to a usual maximum of 300 micrograms once daily.7 Doses up to 400 micrograms once daily may be used on specialist advice.

Monitoring: Monitor U&Es before treatment, weekly for first month and then 3-monthly thereafter. Check lying and standing BP before each dose titration and at least once weekly until dose and condition stable.6,7

Discontinue if:

• Blood pressure in either position increases above 180/100 mm Hg or is considered clinically significant.
• Adverse effects worsen the person’s quality of life e.g. oedema, hypertension

Monitor for signs of developing heart failure or volume overload. Salt restriction and/or potassium supplements may be necessary.
For full details of contraindications, cautions, drug interactions and adverse effects check BNF https://bnf.org.uk  or SPC  https://medicines.org.uk

Adverse effects ⁸

Endocrine effects include menstrual irregularities; development of the Cushingoid state and manifestations of latent diabetes mellitus.
Side-effects can be minimised by using lowest effective dose for minimum period possible.

Midodrine tablets (2.5mg, 5mg)
Licensed for treatment of orthostatic hypotension due to autonomic dysfunction (use for other types of orthostatic hypotension is unlicensed).

Dose/ Administration: Initial dose 2.5mg three times a day, increase if necessary at weekly intervals to maximum of 10mg three times a day.

Last dose should be taken at least 4 hours before bedtime, in order to avoid supine hypertension.⁶
Example of titration regimen

• Week 1: 2.5mg three times a day
• Week 2: 5mg each morning, 2.5mg afternoon, 2.5mg early evening
• Week 3: 5mg each morning, 5mg afternoon, 2.5mg early evening
• Week 4: 5mg three times a day

Titration regimens may vary so refer to specialist advice. Initiating specialists should detail the titration regimen in primary care correspondence as well as carefully explaining the regimen to the person with OH.

Dosing in Renal Impairment
CrCl > 20 ml/min - dose as in normal renal function
CrCl < 20ml/min including dialysis patients- start at 2.5mg twice daily and titrate slowly to a maximum of 10mg three times a day

Monitoring: Check U&Es, LFTs and heart rate before treatment. Monitor lying and standing BP, U&Es and LFTs every 6 months. Check lying and standing BP before each dose titration and at least once weekly until dose and condition stable. Increase dose if symptoms remain poorly controlled. Check for signs or symptoms of bradycardia and symptoms of supine hypertension at each review and at least every 6 months e.g. chest pain, palpitations, shortness of breath, headache and blurred vision and advise patients to self-monitor and report immediately.

Discontinue if:

• Blood pressure in either position increases above 180/100 mm Hg or is considered clinically significant.
• Adverse effects worsen the person’s quality of life

For full details of contraindications, cautions, drug interactions and adverse effects check BNF https://bnf.nice.org.uk/ or Summary of Product Characteristics (SPC) at https://medicines.org.uk

Some patients may be treated with both fludrocortisone and midodrine. Midodrine may potentiate or enhance the hypertensive effects of corticosteroid preparations. Patients being treated with midodrine in combination with mineralocorticoids (e.g. fludrocortisone) and glucocorticoids may be at increased risk of glaucoma/ increased intraocular pressure and should be carefully monitored.

Adverse effects⁸:

Common side effects: nausea, dyspepsia, stomatitis, supine hypertension (dose dependent), paraesthesia, headache, urinary disorders, piloerection, pruritus, chills, flushing, rash

Less common side effects: reflex bradycardia, sleep disorders, restlessness, excitability, irritability; rarely tachycardia, palpitations, hepatic dysfunction; also reported abdominal pain, vomiting, diarrhoea, anxiety, confusion

Supine hypertension: regular monitoring of supine and standing blood pressure is required due to the risk of hypertension in the supine position; treatment must be stopped if supine hypertension is not controlled by reducing the dose. The risk of supine hypertension at night can be reduced by raising the head of the bed. Manufacturer advises that patients report symptoms of supine hypertension (such as chest pain, palpitations, shortness of breath, headache and blurred vision) immediately.