Intervention and alternatives

Intervention and alternatives

This evidence summary addresses the use of oral fludrocortisone acetate tablets (Florinef; E.R. Squibb & Sons) for treating postural hypotension in adults.

Fludrocortisone is a synthetic mineralocorticoid that acts by increasing plasma volume as a result of its sodium-retaining effects, thus increasing cardiac output. It also acts by potentially increasing sensitivity to sympathetic nerve stimulation, leading to an increase in peripheral vascular resistance (Ong et al. 2013).


Postural (or orthostatic) hypotension is a condition in which standing leads to an abnormally large drop in blood pressure, which can result in symptoms such as light-headedness, dizziness, blurring of vision, fainting and falls (Lahrmann et al. 2011). Symptoms resolve as blood pressure returns to normal (for example, on returning to a seated position). Not all people with postural hypotension experience symptoms.

On standing, gravity causes blood to pool in the lower extremities. The autonomic nervous system usually counteracts this by increasing heart rate, cardiac contractility and vascular tone (Freeman et al. 2011). The skeletal muscle in the lower body also contracts to prevent excessive pooling.

The definition of postural hypotension endorsed by the European Federation of Autonomic Societies is a sustained reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg within 3 minutes of standing, or of tilting the body (with the head up) to at least a 60° angle on a tilt table (Freeman et al. 2011). Acute, unexpected, episodic falls in blood pressure while standing, such as those seen in vasovagal syncope, do not satisfy criteria for postural hypotension (Goldstein and Sharabi 2009). The use of fludrocortisone for vasovagal syncope was not the focus of this evidence summary, although the trial by Rowe et al. (2001) included people with neurally mediated hypotension (NMH), which the authors report is also known as vasovagal hypotension, delayed orthostatic hypotension, neurocardiogenic syncope or vasodepressor syncope. Safety data from fludrocortisone use over a mean of 12 months in an observational study of a mixed population are also included. The study included people with 1 or more hypotensive disorders (postural hypotension, vasodepressor carotid sinus syncope and/or vasodepressor neurocardiogenic syncope).

Postural hypotension may be idiopathic or may arise as a result of disorders affecting the autonomic nervous system (for example, Parkinson's disease, multiple system atrophy or diabetic autonomic neuropathy), from a loss of blood volume or dehydration, or because of certain medications such as antihypertensives (Gibbons et al. 2010).

Postural hypotension is more common in older people, and estimates of prevalence range from 5% to 30% of people aged over 65 years (in the general population), up to 60% of people with Parkinson's disease, and up to 70% of people living in nursing homes (Freeman et al. 2011; Lahrmann et al. 2011). It is estimated that about 0.2% of people over 75 years are admitted to hospital with problems relating to postural hypotension (Gibbons et al. 2010).

NICE guidance on transient loss of consciousness in adults and young people advises that, if postural hypotension is suspected after an initial assessment, when the history is typical and there are no features suggesting an alternative diagnosis, then the person should have their blood pressure measured lying and standing (with repeated measurements while standing for 3 minutes). The guidance advises that if postural hypotension is confirmed, the likely causes should be considered and the condition should be managed appropriately. NICE clinical guideline on Parkinson's disease recommends that people with Parkinson's disease should have postural hypotension treated appropriately. Specific management options are not discussed in these guidelines.

NICE guidance on chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) recommends that the head-up tilt test should not be done routinely to aid CFS/ME diagnosis. It also recommends that mineralocorticoids such as fludrocortisone should not be used for treating CFS/ME.

Alternative treatment options

A number of drug and non-pharmacological approaches have been used to treat postural hypotension (Logan and Witham 2012). Non-pharmacological treatments include increasing water and salt intake, or using compression garments or bandages and physical manoeuvres to counter the drop in blood pressure (Gibbons et al. 2010; Logan and Witham 2012).

There are no drugs with marketing authorisation for use in postural hypotension in the UK. Many drugs have been considered or studied for potential use in postural hypotension, including drugs that target the autonomic nervous system (such as midodrine, phenylephrine, ephedrine, pseudoephedrine, droxidopa and phenylpropanolamine), pyridostigmine, domperidone, non-steroidal anti-inflammatory drugs and erythropoietin (Gibbons et al. 2010; Logan and Witham 2012).

Some of these drugs, such as domperidone and pyridostigmine (as well as fludrocortisone) have licences for other indications in the UK, but their use in postural hypotension is off label.

Midodrine does not have UK marketing authorisation for postural hypotension or any other indication. NICE has published an evidence summary on the unlicensed or off-label use of midodrine for treating postural hypotension in adults.

One systematic review concluded that many commonly used interventions for postural hypotension have a limited evidence base to support their use (Logan and Witham 2012).