Neurogenic Orthostatic Hypotension

Neurogenic orthostatic hypotension is a sustained fall in blood pressure on standing (at least 20 mmHg systolic or 10 mmHg diastolic within 3 minutes) due to failure of the autonomic nervous system to produce adequate noradrenaline release. It is a feature of Parkinson disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, diabetic and amyloid neuropathy, autoimmune autonomic ganglionopathy and spinal cord injury.

It affects 30 to 50% of people with Parkinson disease and over 80% with multiple system atrophy.

Pathophysiology. Impaired sympathetic vasoconstriction and venous return on standing cause cerebral hypoperfusion, with a blunted heart rate response.

Dizziness, light headedness, visual blurring, weakness, fatigue, neck and shoulder pain, cognitive slowing, syncope and falls on standing, worse in the morning, after meals, heat and exercise. Supine hypertension is common, and nocturia occurs.

Red flags.

• Recurrent syncope or injurious falls.
• Chest pain or neurological signs on standing.

Measure blood pressure and heart rate lying for 5 minutes, then at 1 and 3 minutes standing. A ratio of heart rate rise to pressure fall under 0.5 beats/min/mmHg suggests neurogenic cause. Tilt table testing, Valsalva manoeuvre and autonomic function tests. Review drugs (antihypertensives, alpha blockers, diuretics, antidepressants, levodopa, dopamine agonists) and exclude hypovolaemia, anaemia, adrenal insufficiency, cardiac causes and bleeding. Ambulatory pressure monitoring detects supine hypertension.

Differential diagnosis.

• Non-neurogenic orthostatic hypotension (drugs, volume depletion).
• Postural tachycardia syndrome and vasovagal syncope.
• Cardiac arrhythmia and valve disease.

Stop or reduce culprit drugs where possible.

Non-drug measures. Fluids 2 to 3 litres daily, salt 6 to 10 g daily, slow positional changes, avoid heat, large meals and alcohol, compression garments (abdominal binder, stockings), head up bed tilt by 10 to 20 degrees, counter manoeuvres (leg crossing, squatting) and graded exercise.

Drugs (stepwise).

• Midodrine 2.5 mg three times daily, increased to 10 mg three times daily (last dose at least 4 hours before bedtime). Avoid with severe heart disease and urinary retention.
• Droxidopa 100 mg three times daily, increased to 600 mg three times daily.
• Fludrocortisone 0.1 mg daily, increased to 0.3 mg daily, with monitoring of potassium, oedema and heart failure.
• Pyridostigmine 30 to 60 mg three times daily, atomoxetine 18 to 40 mg daily, or desmopressin 0.1 to 0.2 mg at night for nocturia in selected cases.

Supine hypertension. Sleep with the head elevated, avoid lying flat in the day, and give a short acting agent at bedtime if above 160 to 180 mmHg systolic (for example losartan 25 mg or hydralazine, or a transdermal glyceryl trinitrate patch removed in the morning).

Post-prandial hypotension. Small, low carbohydrate meals, water before meals and caffeine.

Monitoring. Seated and standing blood pressure, supine pressure, potassium and renal function.

Referral and escalation. Refer to neurology or an autonomic service for refractory disease.