Neurogenic orthostatic hypotension – management update and role of droxidopa

Figures & data

Figure 1 Various mechanisms for maintaining orthostatic normotension.

Table 1 Physiological mechanisms involved in the maintenance of orthostatic normotension

Baroreflex pathway initiated at the carotid sinus and arch of aorta

Venoarteriolar reflex

Myogenic responses

Vestibulospinal reflex

Vasopressin–endothelin–nitrous oxide system

Systemic constrictor effects of renin–angiotensin system

Sodium/volume effects of aldosterone

Table 2 Diseases commonly associated with autonomic dysfunction

Preganglionic autonomic failure

Multiple system atrophy

Parkinson’s disease with autonomic failure

Ganglionic and postganglionic disorders

Pure autonomic failure

Peripheral neuropathies and neuronopathies with autonomic dysfunction

Acute and subacute (preganglionic and postganglionic)

Acute pandysautonomia

Guillain–Barré syndrome

Paraneoplastic pandysautonomia

Others (porphyria, toxins, drugs)

Chronic small-fiber (postganglionic) neuropathies

Diabetes

Amyloidosis

Hereditary (familial dysautonomia, Fabry’s disease)

Subacute or chronic sensory and autonomic ganglionopathies

Paraneoplastic

Sjögren’s syndrome

Other peripheral neuropathies

Infections (human immunodeficiency virus)

Connective tissue disease (systemic lupus erythematosus)

Metabolic-nutritional (alcohol, uremia, vitamin B12 deficiency)

Table 3 Common drugs commonly associated with OH

Antihypertensive agents

ACE inhibitors

Calcium channel blockers

Beta-blockers

Vasodilators

Nitrates

Adrenoceptor blockers

Dopamine receptor agonists

Sympatholytics

Diuretics

Tricyclic antidepressants

Opioids and other sedatives

Monoamine oxidase inhibitor

Chemotherapeutic agents

Abbreviations: OH, orthostatic hypotension; ACE, angiotensin converting enzyme.

Table 4 Investigations of autonomic dysfunction

Assessment of global autonomic function

A. Tests of thermoregulatory function

B. Tests of exocrine and pupillary regulation

C. Tests of gastrointestinal autonomic regulation

D. Tests of genitourinary autonomic regulation

Specific tests for cardiac and vascular autonomic regulation

A. Evaluation of cardiac vagal innervation

1. Heart rate response to deep breathing

2. Heart rate response to Valsalva maneuver

3. Heart rate response to postural change (the 30:15 ratio)

B. Evaluation of cardiovascular sympathetic innervation

1. Cardiovascular response to postural change

2. BP response to Valsalva maneuver

3. Cold pressor test

4. BP response to sustained handgrip maneuver

Specific tests to differentiate preganglionic from postganglionic disorders

1. Supine plasma catechols

2. Neuropharmacologic probes

3. Cardiac sympathetic neuroimaging

Abbreviation: BP, blood pressure.

Table 5 General investigations for autonomic disorders

Blood investigations

1. Full blood count, renal function, calcium panel, liver panel

2. Fasting blood sugars and HbA1c

3. Serum B12 and folate

4. Serum electrophoresis

5. Serological tests for systemic vasculitis

6. Onconeural antibody profile

7. Neuronal autoimmune panel

Electrodiagnostic studies

1. Nerve conduction studies

2. Sympathetic skin response

Imaging studies

1. Magnetic resonance imaging of the brain

2. Positron emission tomography for underlying malignancy if the cause is not obvious with associated symptoms

Histological studies

1. Intradermal nerve fiber density

2. Fat aspirate with Congo red staining

Abbreviation: HbA_1c, glycated hemoglobin.

Table 6 Treatment of OH

Nonpharmacological

Adequate fluid and salt intake

Water boluses of up to 500 mL early morning

Small frequent meals

Limit alcohol

Raise head of the bed to 30°

Physical counter-maneuvers to increase venous return – tip toeing, leg crossing, squatting

Custom-fitted elastic stockings and abdominal binders

Pharmacological

I. Agents that act by stimulating the adrenergic receptors

Midodrine

Droxidopa

Sympathomimetic agents

Acetylcholinesterase inhibitors

II. Agents that act by increasing the central blood volume

Fludrocortisone

Erythropoietin

Vasopressin

Abbreviation: OH, orthostatic hypotension.