Orthostatic hypotension (OH) is a common condition in the elderly. It is associated with significant risk of morbidity and independently predicts all cause mortality. It is defined as a decrease in systolic blood pressure (BP) of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg within three minutes of an erect posture (e.g. upon standing), relative to a supine blood pressure reading. OH is most prevalent in, though not limited to, the elderly population; it is characterized by a variety of clinical features, including impaired cognition and speech, disturbed emotion, falls and fractures, and increased risk of cerebrovascular and cardiovascular events. It occurs in approximately 30% of adults over 65, and up to 70% of elderly nursing home residents. In addition to its unpleasant and disabling symptoms, people with OH are more likely to be physically frail which results in decreased functional capacity, a factor that is often overlooked during evaluation of older patients.

Pathogenesis

OH often results as a consequence of inadequate autonomic compensation during postural change. It depends on a combination of mechanisms, such as inadequate intravascular volume, dysfunction of the autonomic nervous system, reduction of venous return, and defective heart rate compensation. Age-related changes that affect normal blood pressure regulation include changes in baroreceptor reflex sensitivity, decreased renal salt and water conservation, and impairment in diastolic filling. These factors contribute to OH, along with the presence of multiple chronic diseases and the combination of various drug therapies.

Aetiology

The causes of OH can be either acute or chronic. Acute OH commonly develops over a short period of time and is more often symptomatic at the onset. It can be caused by adrenal crisis, brady/tachyarrhythmia, myocardial infarction, sepsis, dehydration and some medications. In contrast, chronic OH develops over time and the patient is usually initially asymptomatic. It can result from physiological and pathological causes. Physiological causes include baroreceptor insensitivity, diastolic dysfunction and hypertension. Pathological causes include the central nervous system, brain stem lesions, Lewy body dementia, multiple cerebral infarctions, multiple system atrophy, myelopathy, Parkinson’s disease, the peripheral nervous system, amyloidosis, alcoholisms, pure autonomic failure and pernicious anaemia.

Clinical Features

Patients experiencing OH may be symptomatic or asymptomatic. Although a patient may be asymptomatic, OH remains an important risk factor for future falls and syncope, and should be managed where possible. Common signs and symptoms of OH include: light headedness/dizziness and confusion, decreased cognition and disturbed speech, weakness and lethargy, visual changes (blurred vision, tunnel scotomas, greying of colours), syncope, palpitations, nausea and tendency to fall.

Management

Treatment of OH in the elderly can be challenging due to the presence of multiple co-morbid conditions with non-specific signs and symptoms. Instead of aiming to achieve arbitrary blood pressure goals, the goal of treatment should be directed towards reducing the incidence and severity of postural symptoms, correcting underlying causes, improving the patient’s functional status, and reducing the risk of complications. Broadly, interventions can be divided into non-pharmacological and pharmacological approaches.

Non-pharmacological Management

Generally, non-pharmacological measures should be the first-line approach to treatment. The first management step involves removing any medication that could contribute to OH. Table 1 lists some common drug contributors to OH.

Table 1: Common drug classes associated with orthostatic hypotension

Therapeutic Class

Therapeutic Subgroup/Drug

Anaesthetics

Antidepressants

MAO inhibitors, tricyclic antidepressants

Antihypertensives

ACE inhibitors, Alpha1-adrenergic antagonists, Angiotensin II antagonists, Beta blockers, Calcium channel blockers, Diuretics, Vasodilators

Antiparkinsonian agents

Dopamine agonists, Levodopa

Antipsychotics

Atypical antipsychotics, Chlorpromazine

Narcotics

Nitrates

Glyceryl trinitrate

Other drugs

Alcohol, Marijuana

Phosphodiasterase-5 inhibitors

Sildenafil, Tadalafil, Vardenafil

Sedatives

 

 
Other non-pharmacological management options include:

  • Taking causative medications at bedtime, (e.g. antihypertensives)
  • Standing or sitting up gradually, especially after prolonged inactivity or bed rest
  • Avoiding large carbohydrate meals and limiting alcohol intake
  • Ensuring adequate hydration (minimum 1.25-2.50L fluid per day)
  • Sodium supplementation by increasing salt intake or salt tablets
  • Abdominal binders and waist-high compression stockings
  • Raising head of bed by 10-20 degrees at night
  • Exercise programs and physical manoeuvres (e.g. standing with legs crossed, bending forward squatting, dorsiflexion of feet)

Pharmacological Management

Pharmacological treatment may be indicated when a patient does not respond adequately to non-pharmacological management. Table 2 summarises medications used in treatment of orthostatic hypotension.

Table 2: Pharmacological agents for the management of orthostatic hypotension

Drug

Fludrocortisone

Midodrine

Octreotide

Mode of action

Synthetic mineralocorticoid. Reduces salt loss and expands blood volume

Peripheral selective alpha1-adrenergic agonist. Increases standing systolic BP through constriction of blood vessels

Somatostatin analogue. Reduces post-prandial hypotension via inhibiting release of gastrointestinal peptides, leading to splanchnic vasoconstriction

Dosage

Initially 0.1mg daily, increase by 0.1mg weekly. Max dose: 1mg daily

Initially 2.5mg three times daily, titrate in 2.5mg/dose increments weekly. Max dose: 10mg three times daily

Subcutaneous injection, 25-50mcg half an hour before meals

Contraindications

Hypersensitivity, systemic fungal infections

Coronary heart disease, urinary retention, thyrotoxicosis, acute renal failure, phaeochromocytoma

Hypersensitivity. Use cautiously in patients with diabetes, insulinoma and gastroenteropancreatic tumours.

Common adverse effects

Headache, supine hypertension, congestive heart failure, oedema, hypokalaemia

Piloerection, pruritus, paraesthesia, supine hypertension

Nausea, abdominal pain, flatulence, vomiting, hyperglycaemia, hypoglycaemia

 

In patients who do not respond adequately to non-pharmacological treatment, specific drug therapy may be indicated. Fludrocortisone is a valuable first-line therapy for OH. Should a patient remain symptomatic on fludrocortisone, a sympathomimetic drug such as midorine can be added to therapy. The availability of midodrine in Australia is currently restricted to the Special Access Scheme. In the United States, it is the only approved peripheral selective alpha1-adrenergic agonist for the treatment of orthostatic hypotension. It is also approved for use in several EU countries, including Germany, France, Ireland, Italy and Spain.

Other drugs that have been trialled in the treatment of OH include pyridostigmine, erythropoietin, indomethacin, pseudoephedrine, caffeine, clonidine, dihydroergotamine, desmopressin and yohimbine; however the efficacy and safety of these therapies has not been adequately established. Further large randomised clinical trials are required to support the effectiveness of current therapeutic management options and to identify novel treatment approaches.

Referral to a Specialist

Consultation with a geriatrician should be sought for frail elderly patients and those with multiple co-morbid conditions including cognitive decline, failure of standard therapy, any symptom-related complications or lack of social support. Referral to a cardiologist is indicated for patients with uncontrolled supine hypertension despite standard therapy, advanced symptomatic coronary artery disease, severe heart failure and those with recent onset of tachy/bradyarrhythmias. A neurological consult would be recommended if specialized autonomic testing is required in patients with an unclear diagnosis and progressive autonomic failure.

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