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Classification

	Clinical definition				Pathophysiology
	BP fall	Time line for symptoms after standing	Symptoms	Resolving
Initial orthostatic hypotension (iOH)	Transient BP decrease of >40 mmHg systolic or >20 mmHg diastolic	5-15 s after standing	Yes	Symptoms resolve by 20s	Healthy adolescents More pronounced during active standing leading to venous pooling
Neurogenic orthostatic hypotension (nOH)	Sustained BP decrease of >20 mmHg systolic or >10 mmHg diastolic	Within 3 mins	With or without		Impaired noradrenergic responses to the Valsalva maneuver. Failure of noradrenergic nerves to maintain BP in response to standing.
Delayed orthostatic hypotension (dOH)	Sustained BP decrease of >20 mmHg systolic or >10 mmHg diastolic	After 3 mins	Yes		Similar to nOH Early or milder form of nOH
Neurally mediated syncope (vOH)	BP declines over 1–3 min.	After 7s when BP falls below 50mm	Yes		Paroxysmal withdrawal of sympathetic vasopressor tone, often during prolonged standing
Cardiovascular orthostatic hypotension (cOH)

Non-Pharmacological methods	Mechanism of alleviating hypotension	Recommendations
Elastic stockings	Reduce venous pooling in the splanchnic and mesenteric circulations.	Elastic stockings expanding up to the waist are recommended. Leg compression alone is not considered effective. Due to the minor venous capacitance of legs relative to the abdomen. Separate abdominal and leg compression is recommended to avoid patient's discomfort.
Physical Maneuvers	Transiently increase venous return and peripheral vascular resistance	Contraction of a group of muscles Leg-crossing Toe raising Bending at the waist
Head up tilt sleeping	Enhance orthostatic tolerance upon the first-morning rise	Results in reduction in supine hypertension, pressure-natriuresis
Intravascular volume	Tubular loss of salt and fluid Decreased vascular tone creates relative hypovolemia	Volume expansion can alleviate symptoms even in the presence of normal intravascular volume. 2 liters of water and 6 g of salt Twenty-four-hour urine collection is helpful to guide treatment and follow-up
Intake of cold water	Increase systolic orthostatic hypotension by more than 30 mmHg Via gastropressor response	Rapid drinking of approximatively 500 mL of cold water, independent of daily water intake

Drop of systolic BP > 20 mmHg (30 for hypertensive patients)

Symptomatic

Asymptomatic

Non-pharmacological treatment

Observation and follow-up

Persistance of symtoms

Pharmacological Treatment

No supine hypertension or chronic heart failure

Supine hypertension or chronic heart failure:

Fludrocortisone Midodrine

Midodrine

Stepwise approach

Steps to approach a patient

When we should suspect orthostatic hypotension? Unexplained fall/syncope Typical symptoms Patient history Current pharmacological treatment

Initial assessment (outpatient clinic. ED and hospital): Physical examination Laboratory assessment Bedside BP supine/standing test (after 1-3.5 min) Cardiac assessment Neurological assessment

Initial Therapy

• Preferred regimen (1): Fludrocortisone acetate at a dose of 0.1 mg per day, administered in the morning, which can eventually be increased up to 0.3 mg per day.
  • Considered first-line regimen for hypotension in the absence of heart failure and supine hypertension
• Preferred regimen (2): Midodrine 2.5 to 10 mg three times a day.
  • Max dose should not exceed 40 mg/day.
• Preferred regimen (2): Droxidopa starts at 100 mg and escalates to 600 mg three times per day.
  • Patients should not take droxidopa within four to five hours of bedtime in order to limit supine hypertension.

Secondline Therapy

• Preferred regimen (1): Erythropoietin is administered SC or IV at doses between 25 to 75 units/kg three times a week.
• Preferred regimen (1): Methylxanthine caffeine 100 to 250 mg three times a day with meals.
• Preferred regimen (1): Pyridostigmine initiated at a dose of 30 mg three times daily, up to a maximum dose of 90 mg three times daily.
• Preferred regimen (1): Nonsteroidal anti-inflammatory drugs are rarely effective as monotherapy
  • They can supplement treatment with fludrocortisone or a sympathomimetic agent.

Thirdline Therpay

• Preferred regimen (1): Atomoxetine
• Preferred regimen (1): Vasopressin analogs (desmopressin (DDAVP))
• Preferred regimen (1): Yohimbine a single dose of yohimbine (5.4 mg).
  • Yohimbine has limited availability in the United States.
• Preferred regimen (1): Somatostatin subcutaneous doses range from 25 to 200 mcg.
• Preferred regimen (1): Ergotamine-caffeine (1 mg/100 mg) up to twice-daily dosing in patients with orthostatic hypotension.
• Preferred regimen (1): Metoclopramide and domperidone