Orthostatic hypotension

Definition and Overview

Orthostatic hypotension (OH) is defined as a condition in which systolic blood pressure falls by more than 20 mmHg or diastolic blood pressure falls by more than 10 mmHg within 3 minutes after switching from a supine position to a standing position. This diagnostic standard was established in an international consensus published by Freeman et al. in 2011, and is still used worldwide.

Normally, when a person stands up, about 500 to 1,000 mL of blood is stored in the lower limbs and abdominal veins due to gravity. At this time, baroreceptors in the carotid sinus and aortic arch detect the drop in blood pressure, activate the sympathetic nerves, and compensate for the blood pressure by constricting peripheral blood vessels and increasing heart rate. Orthostatic hypotension occurs when there is an abnormality in any step of this baroreflex pathway.

Epidemiologically, the prevalence of orthostatic hypotension significantly increases with age. The prevalence is approximately 5-6% in the general adult population, but increases to 15-20% in people aged 65 or older. It has been reported to reach 30% in the elderly group over 80 years of age. The prevalence is higher in hospitalized patients, reported to be approximately 60%. Orthostatic hypotension occurs in approximately 30 to 50% of Parkinson's disease patients and in approximately 20 to 25% of diabetes patients.

Orthostatic hypotension is largely divided into neurogenic orthostatic hypotension (nOH) and non-neurogenic orthostatic hypotension. Neurogenic orthostatic hypotension is caused by structural and functional damage to the autonomic nervous system itself, while non-neurogenic orthostatic hypotension is caused by factors external to the autonomic nervous system, such as dehydration, bleeding, and drugs. This distinction is key to establishing treatment strategies.

Initial orthostatic hypotension is a temporary drop in systolic blood pressure of 40 mmHg or more within 15 seconds after standing, and is not uncommon in young people. Delayed orthostatic hypotension, in which blood pressure drops only after 3 minutes after standing, may be a sign of early autonomic dysfunction.

cause

Causes of orthostatic hypotension are classified into three categories: neurological causes, non-neurological causes, and drug-induced causes.

Neurogenic causes

This is a case where the pressure receptor reflex does not function properly due to structural and functional damage to the autonomic nervous system.

• Parkinson's disease: Orthostatic hypotension occurs in 30-50% of patients, and the main mechanism is decreased norepinephrine secretion from peripheral sympathetic nerves. Levodopa, a Parkinson's disease treatment drug, and dopamine agonists themselves can also worsen orthostatic hypotension.
• Multiple system atrophy (MSA): Occurs due to degeneration of the central autonomic control nucleus, and severe orthostatic hypotension occurs in almost all patients.
• Pure autonomic failure (PAF): Occurs due to selective degeneration of peripheral sympathetic neurons. It is characterized by a significantly low concentration of norepinephrine in the blood.
• Diabetic autonomic neuropathy: Causes orthostatic hypotension in 20-25% of diabetic patients. It is preceded by small fiber neuropathy, and the longer the disease period, the higher the frequency.
• Amyloidosis: Abnormal proteins are deposited on autonomic nerve fibers, blocking nerve conduction.
• Autoimmune autonomic ganglionopathy: Caused by autoantibodies against nicotine receptors in autonomic ganglia.
• Spinal cord injury: In damage to areas above the pleural effusion (T6), sympathetic nerve outflow is blocked, resulting in orthostatic hypotension.

Non-neurogenic causes

The autonomic nervous system itself is normal, but it occurs due to a decrease in circulating blood volume or blood vessel relaxation.

• Dehydration: Caused by loss of body fluids due to fever, diarrhea, vomiting, and excessive sweating.
• Hemorrhage: A decrease in circulating blood volume due to acute or chronic bleeding.
• Adrenal insufficiency: Reduced secretion of cortisol and aldosterone makes it difficult to maintain blood pressure.
• Long-term bed rest: Just 2 to 3 weeks of bed rest can weaken baroreceptor reflex function and cause orthostatic hypotension.
• Postprandial orthostatic hypotension: This is a form in which blood pressure drops as blood flow to the digestive tract after a meal, and is common in elderly people.

drug induced

Drugs are the most common correctable cause of orthostatic hypotension. Orthostatic hypotension is reported in approximately 15-20% of patients taking antihypertensive drugs.

• Alpha-blockers: Representative treatments for benign prostatic hyperplasia such as prazosin, doxazosin, and tamsulosin. It inhibits peripheral blood vessel constriction and prevents blood pressure compensation when standing.
• Diuretics: Reduce circulating blood volume by excreting water and sodium from the body.
• Calcium channel blockers, ACE inhibitors, ARBs: May cause orthostatic hypotension due to their vascular relaxant effect.
• Tricyclic antidepressant: Has alpha-1 receptor blocking effect.
• Dopamine agonists: Drugs used to treat Parkinson's disease cause vasodilation.
• Nitrates: Reduce venous return by dilating blood vessels.
• Opioids: Cause sympathetic depression and vascular relaxation.

symptoms

Symptoms of orthostatic hypotension are caused by a decrease in cerebral blood flow when standing, and most improve within a few minutes when lying down or sitting.

Cerebral hypoperfusion symptoms

• Dizziness: The most common symptom, it occurs immediately after standing up or within seconds to minutes after standing.
• Visual blurring: A symptom in which the vision before the eyes becomes dark or blurred.
• Syncope: Loss of consciousness when cerebral blood flow suddenly decreases. Orthostatic hypotension accounts for approximately 15-30% of the causes of syncope in the elderly.
• Presyncope: A feeling of loss of consciousness or a pounding sensation in the head.
• Decrease in cognitive function: Decreased concentration and poor judgment may occur when standing up.

Musculoskeletal symptoms

• Pain or stiffness in the back of the neck and shoulders: This is caused by ischemia in the trapezius region and is called 'coat-hanger pain'. This is a characteristic symptom of neurogenic orthostatic hypotension.
• Back pain: Caused by decreased blood flow to the muscles around the spine when standing up.

systemic symptoms

• Feeling of whole body weakness: Complains of overall loss of strength when standing up.
• Fatigue: In some cases, it may persist chronically.
• Shortness of breath: May occur due to decreased cardiac output when standing.

Factors that worsen symptoms

• Immediately after waking up in the morning: Plasma volume has decreased due to nocturnal diuresis.
• After a meal: As blood flow is concentrated in the digestive tract, blood pressure drops further.
• Hot environment: Venous return is reduced due to skin vasodilation.
• Prolonged standing: Blood retention in the lower extremities due to gravity accumulates.
• Alcohol: The vasodilator effect of alcohol worsens orthostatic hypotension.
• Dehydration: Circulating blood volume decreases due to fever, diarrhea, or lack of water intake.

diagnosis

Diagnosis of orthostatic hypotension is made by objectively confirming changes in blood pressure when standing and determining the cause.

active standing test

This is the easiest screening test to perform in an outpatient setting. After resting the patient lying down for 5 minutes, blood pressure is measured, and blood pressure and heart rate are repeatedly measured at 1 and 3 minutes after standing. Orthostatic hypotension is diagnosed when a drop in systolic blood pressure of more than 20 mmHg or diastolic blood pressure of more than 10 mmHg is confirmed. Heart rate response is important in distinguishing between nervous and non-neurotic symptoms. In non-neurogenic orthostatic hypotension, a compensatory heart rate increase (more than 15 beats per minute) is observed, but in neurogenic orthostatic hypotension, the heart rate increase is insufficient.

Standing tilt table inspection

The patient is fixed on an automatic tilt table, tilted at an angle of 60 to 70 degrees, and continuous changes in blood pressure and heart rate are observed for 20 to 45 minutes. In the active standing test, the pumping action of the lower limb muscles is involved, but in the tilt-table test, this can be excluded and pure autonomic reflex function can be evaluated. It is also useful in diagnosing delayed orthostatic hypotension.

24-hour ambulatory blood pressure monitoring

Identify patterns of blood pressure fluctuations during daily life. It is essential for the identification of supine hypertension in patients with orthostatic hypotension, and is also used to monitor the effectiveness and side effects of drug treatment.

Autonomic function test

• Heart rate variability (HRV) analysis: Non-invasively evaluates the balance between the sympathetic and parasympathetic nerves.
• Valsalva maneuver: evaluates sympathetic function through four-step pattern analysis of blood pressure response. In normal people, a stage 4 overshoot occurs where blood pressure rises above the baseline level after the end of the operation, but this response is lost in neurogenic orthostatic hypotension.
• Quantitative Sudomotor Axon Reflex Test (QSART): Estimates the extent of autonomic impairment by assessing sweat function.

Differential test for cause

• Blood tests: Check for anemia, blood sugar, glycated hemoglobin, thyroid function, cortisol, vitamin B12, etc.
• Plasma norepinephrine concentration: Measured in both lying and standing positions and used to differentiate neurogenic orthostatic hypotension. In neurogenic orthostatic hypotension, the rise in norepinephrine upon standing is insufficient.
• Medication review: Evaluate all medications currently being taken for their potential to cause orthostatic hypotension.

treatment

Treatment of orthostatic hypotension involves step-by-step correction of the cause, non-drug therapy, and drug therapy.

Cause Correction

If drug-induced orthostatic hypotension is suspected, first consider reducing or changing the causative drug. If dehydration is the cause, fluid supplementation is necessary, and if endocrine causes such as adrenal insufficiency are confirmed, hormone replacement therapy is performed. In diabetic patients, controlling blood sugar levels helps slow the progression of autonomic neuropathy.

Non-drug treatment

Non-pharmacological treatment is the basic basis of treatment for all patients with orthostatic hypotension.

• Water intake: Drink 2 to 3 liters of water per day. It has been reported that drinking 500 mL of water immediately after waking up or before a meal using a water bolus method causes the systolic blood pressure to rise to about 20 mmHg after about 5 to 20 minutes.
• Salt intake: If you do not have a contraindication disease (heart failure, kidney failure), it is recommended to consume 6 to 10 g of salt per day. Salt increases water retention in the body and contributes to maintaining circulating blood volume.
• Compression stockings and belly bands: Reduce venous blood retention in the lower extremities and abdomen and increase venous return to the heart. Compression stockings rated at 30 to 40 mmHg that go up to the thigh are recommended.
• Posture management: Sleeping with the head of your bed raised 10 to 15 degrees (approximately 15 to 23 cm) can reduce nocturnal diuresis and relieve morning orthostatic hypotension. Avoid sudden changes in posture and perform physical countermaneuver such as crossing lower limbs or squatting before standing.
• Small, frequent meals: Avoiding large meals and eating small, frequent meals can reduce postprandial low blood pressure.

medication

Drugs are added when symptoms are not adequately controlled with non-drug therapy.

• Midodrine: A selective alpha-1 adrenergic receptor agonist that constricts peripheral blood vessels and prevents a decrease in blood pressure when standing. In a double-blind randomized controlled trial, systolic blood pressure was maintained approximately 22 mmHg higher in the midodrine 10 mg administration group when standing compared to the placebo group, and dizziness symptoms were significantly reduced. The dosage starts at 2.5 mg and increases up to a maximum of 10 mg three times a day. The last dose should be completed 4 hours before bedtime to be careful of the risk of high blood pressure while lying down.
• Fludrocortisone: A synthetic mineralocorticoid that increases circulating blood volume by promoting sodium reabsorption in the kidneys. The dosage is 0.1 to 0.3 mg/day. Side effects such as hypokalemia, edema, and supine hypertension should be monitored.
• Droxidopa: A norepinephrine precursor that is converted to norepinephrine in the body and complements the function of the sympathetic nervous system. This is a drug approved by the US FDA for neurogenic orthostatic hypotension. In clinical trials, it increased systolic blood pressure by about 10 to 15 mmHg when standing up and significantly reduced dizziness and pre-syncope symptoms.
• Pyridostigmine: An acetylcholinesterase inhibitor that enhances nerve transmission in the autonomic ganglia. It has the characteristic of selectively raising blood pressure only when standing, so the risk of hypertension while lying down is low. It is used for mild orthostatic hypotension or combination therapy.
• Atomoxetine: A norepinephrine reuptake inhibitor. Research results have reported that it is more effective in increasing blood pressure when standing than midodrine in neurogenic orthostatic hypotension.

Neuromodulation treatment

• Stellate ganglion block: Local anesthetic is injected into the cervical sympathetic ganglion to rebalance autonomic nervous system control.
• Transcranial Magnetic Stimulation (TMS): Used to control the function of the autonomic nervous system through non-invasive brain stimulation.

supine hypertension

Approximately 50% of patients with orthostatic hypotension, especially neurogenic orthostatic hypotension, suffer from supine hypertension. This creates a paradoxical situation in which hypotension when standing and hypertension in the supine position alternate in the same patient.

Supine hypertension is defined as systolic blood pressure over 140 mmHg or diastolic blood pressure over 90 mmHg in the supine position. Persistent supine hypertension may increase the risk of left ventricular hypertrophy, kidney damage, and cerebrovascular disease.

The management principles are as follows.

• Elevating the head of the bed (10 to 15 degrees) lowers nighttime blood pressure and relieves morning orthostatic hypotension.
• Avoid taking vasopressors such as midodrine and fludrocortisone before bedtime.
• Short-acting antihypertensive drugs (nitroglycerin patch, cilazocin, etc.) can be used at night, but the risk of falling due to orthostatic hypotension must be considered when walking to the bathroom at night.
• A carbohydrate snack before bed may help lower blood pressure slightly by increasing blood flow to the intestines.

Simultaneous management of orthostatic hypotension and supine hypertension is one of the most clinically challenging challenges because of the pursuit of conflicting goals. It requires detailed adjustment tailored to the individual's symptom pattern and blood pressure profile.

life guide

Daily management of patients with orthostatic hypotension is as important as drug treatment, and consistent practice of living rules is the key to controlling symptoms.

standing tips

• Do not stand upright while lying down. First, sit on the edge of the bed and lower your legs for 1 to 2 minutes, then stand up slowly.
• Immediately after standing up, cross your legs or perform physical countermeasures that apply strength to your thighs.
• When you have to stand for a long time, periodically repeat tiptoe lifting and leg muscle contraction.
• Be especially careful when waking up to the bathroom. It is also a good idea to place a portable toilet next to your bed at night.

hydration and diet

• Drink 2 to 3 liters of water a day in frequent portions.
• Drinking 500 mL of water immediately after waking up and 30 minutes before a meal has a boosting effect.
• Maintain adequate salt intake with your doctor's approval. Another method is to use salt tablets.
• Avoid overeating and eat small portions frequently to prevent post-meal low blood pressure.
• Limit alcohol as it causes vasodilation and dehydration.

environmental management

• Hot baths, saunas, and hot springs dilate peripheral blood vessels and worsen orthostatic hypotension. It is safe to take short showers with lukewarm water.
• Avoid prolonged activity in hot and humid environments.
• Caffeine can help maintain blood pressure in small amounts (1 to 2 cups of coffee), but it can also cause dehydration due to its diuretic effect, so it should be adjusted depending on the individual.

exercise

• Regular exercise is beneficial in managing orthostatic hypotension by improving circulating blood volume and vascular reactivity.
• In the early stages of severe symptoms, start with non-orthostatic exercise such as cycling or swimming while lying down.
• Gradually add orthostatic exercises such as walking or light jogging.
• It is essential to drink enough water before and after exercise.

monitoring

• Periodically measure and record blood pressure in lying and standing positions with a home blood pressure monitor.
• Keep a symptom diary to identify exacerbating factors and patterns over time.
• If new symptoms occur or syncope recurs, visit a specialist early.