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Guideline:

EFNS guidelines on the diagnosis and management of orthostatic hypotension

National Guideline Clearinghouse (NGC). Guideline summary: EFNS guidelines on the diagnosis and management of orthostatic hypotension In: National Guideline Clearinghouse (NGC) [Web site]. Rockville (MD): cited 2006 Sep. Available: http://www.guideline.gov.

Bibliographic Source(s)

Lahrmann H Cortelli P Hilz M Mathias CJ Struhal W Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol 2006 Sep;13(9):930-6. [50 references] PubMed

Guideline Status

This is the current release of the guideline.

These guidelines will be updated when substantial new data pertaining to the management of orthostatic hypotension (OH) become available.

Guideline Category

Diagnosis
Evaluation
Management
Treatment

Intended Users

Physicians

Guideline Objective(s)

To provide physicians with evidence based guidelines for clinical and laboratory diagnostic workup and therapeutic management of orthostatic hypotension (OH)

Target Population

Patients with orthostatic hypotension (OH)

Interventions and Practices Considered

Diagnosis/Evaluation

Structured history taking
Detailed physical and neurological examination
12-lead electrocardiogram (ECG)
Routine laboratory testing
Blood pressure (BP) testing in supine and upright positions
Cardiologic referral if indicated
Active standing or head-up tilt (HUT) with assessment of BP and heart rate for 3 min
Autonomic nervous system screening tests and other investigations depending on etiology of the underlying disorder

Management/Treatment

Individualized therapy
Patient education about various factors that influence BP
Carefully controlled and individualized exercise training (swimming aerobics cycling and walking)
Self-monitoring of blood pressure (BP)
Physical measures including leg crossing squatting elastic stockings and abdominal compression bands
Increased water and salt ingestion
Pharmacological treatment including fludrocortisone midodrine or ephedrine dihydroxyphenylserine (DOPS) subcutaneous octreotide
Management of supine hypertension if needed

Note: The following interventions were considered but not recommended: pharmacological provocation during HUT with sublingual nitro-glycerine or intravenous isoproterenol to diagnose orthostatic hypertension (OH); combination of HUT and physiological measures such as lower body negative pressure application to diagnose OH; cardiac pacing; certain medications such as yohimbine dihydroergotamine desmopressin and others may be used in selected cases.

Major Outcomes Considered

Effectiveness of diagnosis/evaluation
Effectiveness of management/treatment
Functional capacity and quality of life
Side effects of medications

Methods Used to Collect/Select Evidence

Searches of Electronic Databases

Description of Methods used to Collect/Select the Evidence

Electronic search strategies used the following databases: Cochrane library PubMed Medline and various internet search routines for English publications. Key search terms included: 'orthostatic hypotension' 'syncope' 'hypotension' and 'therapy' 'treatment' or 'diagnosis' and first year availability of each referenced literature database until March 2005. References classified by evidence levels were selected by one individual and checked by another investigator.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Evidence Classification Scheme for a Diagnostic Measure

Class I: A prospective study in a broad spectrum of persons with the suspected condition using a "gold standard" for case definition where the test is applied in a blinded evaluation and enabling the assessment of appropriate tests of diagnostic accuracy

Class II: A prospective study of a narrow spectrum of persons with the suspected condition or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls where test is applied in a blinded evaluation and enabling the assessment of appropriate tests of diagnostic accuracy

Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum and where test is applied in a blinded evaluation

Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)

Evidence Classification Scheme for a Therapeutic Intervention

Class I: An adequately powered prospective randomized controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:

Randomization concealment
Primary outcome(s) is/are clearly defined
Exclusion/inclusion criteria are clearly defined
Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences

Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized controlled trial in a representative population that lacks one criteria a–e

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population where outcome assessment is independent of patient treatment

Class IV: Evidence from uncontrolled studies case series case reports or expert opinion

Methods Used to Analyze the Evidence

Systematic Review

Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations

Expert Consensus

Description of Methods Used to Formulate the Recommendations

Where there was a lack of evidence but consensus was clear the Task Force has stated their opinion as good practice points (GPPs).

Rating Scheme for the Strength of the Recommendations

Rating of Recommendations for a Diagnostic Measure

Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent convincing class II studies.

Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.

Rating of Recommendations for a Therapeutic Intervention

Level A rating (established as effective ineffective or harmful) requires at least one convincing class I study or at least two consistent convincing class II studies.

Level B rating (probably effective ineffective or harmful) requires at least one convincing class II study or overwhelming class III evidence.

Level C rating (possibly effective ineffective or harmful) requires at least two convincing class III studies.

Good Practice Points (GPPs) Where there was a lack of evidence but consensus was clear the Task Force has stated their opinion as good practice points.

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation

Peer Review

Description of Method of Guideline Validation

The guidelines were validated according to the European Federation of Neurological Societies (EFNS) criteria (see "Availability of Companion Documents" field in this summary).

Major Recommendations

The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C Good Practice Point [GPP]) are defined at the end of the "Major Recommendations" field.

Diagnostic Strategies

Protocol

Orthostatic testing should take place in a quiet room at a temperature between 20 and 24 degrees C. The patient should rest while supine for ideally 5 minutes before head up tilting test (HUT) is started. Emptying the bladder before testing is recommended.
Passive HUT to an angle between 60 degrees and 80 degrees for 3 minutes is recommended for the diagnosis of orthostatic hypotension (OH).
HUT is considered positive if systolic blood pressure (BP) falls below 20 mmHg and diastolic BP below 10 mmHg of baseline. If symptoms occur the patient should be tilted back to the supine position immediately.
Measurement of plasma noradrenaline levels while supine and upright may be of value.
In contrast with cardiologic guidelines pharmacological provocation with sublingual nitro-glycerine or intravenous isoproterenol is not recommended to diagnose OH as it reduces sensitivity and will result in false positive outcomes.
Combination of HUT and physiological measures such as lower body negative pressure application as used in neurally mediated syncope is not recommended for diagnosis of OH.

HUT is a safe procedure for the diagnosis of OH. However as syncope and arrhythmias have been described the investigating staff should be adequately trained to recognize such problems. Resuscitation equipment and a team experienced in cardiac life support should be available at short notice (GPP).

Level C Recommendations

Structured history taking
Detailed physical examination
12-lead electrocardiogram (ECG) recording
Routine laboratory testing
BP measurements while supine and upright
Cardiologic referral if heart disease or abnormal ECG is present or suspected
Active standing or head-up tilt (HUT) ideally with continuous assessment of BP and heart rate (HR) for 3 min
Further autonomic nervous system (ANS) screening tests with other appropriate investigations depending on the possible aetiology of the underlying disorder

Management

Elevated environmental temperatures a hot bath or shower and sauna should be avoided as they cause venous pooling. Prolonged recumbence during daytime and sudden head up postural change particularly in the morning when BP may be lowered by nocturnal polyuria should be avoided. Post-prandial hypotension may increase orthostatic hypotension (OH) (vasodilatation in splanchnic vessels). Large meals especially carbohydrate rich and alcohol should be avoided. A carefully controlled and individualized exercise training (swimming aerobics and if possible cycling and walking) often improves OH (GPP)

Supine Hypertension

Supine hypertension may be a problem resulting from medication and/or being part of the disease. Therefore 24 hour measurement of BP is best before and if needed after starting a new therapy. Patients may self-monitor BP daily at about the same time and when they experience symptoms. Pressor medications should be avoided after 6:00 pm and the bed head elevated (20–30 cm). On occasion short acting antihypertensive drugs may be considered (e.g. nitro-glycerine sublingual) (GPP).

Non-Pharmacological Treatment

Avoidance of factors that may induce OH is recommended first line particularly in mild forms. Educating the patients and carers on the mechanisms of OH is important. The next step includes a range of non-pharmacological strategies.

Patients should be advised to move to head-up position slowly sit on the edge of the bed for some minutes after recumbence and activate calf muscles while supine. Physical counter manoeuvres can be applied immediately at the onset of pre-syncopal symptoms. They need to be explained and trained individually. In case of motor disabilities and compromised balance as in the cerebellar forms of multiple system atrophy (MSA) programmes with appropriate aids have to be developed. Leg crossing with tension of the thigh buttock and calf muscles (party position) bending over forward to reduce the orthostatic difference between the heart and brain and compress the splanchnic vessels by increasing abdominal pressure squatting to reduce blood pooling are effective in temporarily reducing OH. Not all patients can perform these manoeuvres and sitting or lying down and using a cane that can be folded into a tripod chair are useful. Elastic stockings and abdominal compression bands reduce venous pooling and have been shown effective in small studies. Sleeping with elevation of the head-end of the bed (20 to 30 cm) particularly in combination with low dose fludrocortisone improves OH.

To compensate for renal salt loss a liberal intake of salt at least 8 g (150 mmol) of sodium chloride daily if needed as salt tablets (starting dose 500 mg three times a day (t.i.d.) are recommended. Water repletion (2 to 2.5 l/day) is important while 500 mL of water is effective in rising BP immediately.

Cardiac pacing is not recommended in neurogenic OH.

Pharmacological Treatment

Fludrocortisone

Level C Recommendations

Fludrocortisone as first line drug-monotherapy of OH (0.1 to 0.2 mg/day)
Full benefit requires a high dietary salt and adequate fluid intake
Combination of a high salt diet head-up tilt sleeping (20 to 30 cm) and a low dose of fludrocortisone (0.1 to 0.2 mg) is an effective means of improving OH

Mild dependent oedema can be expected and fludrocortisone should be used with caution in patients with a low serum albumin. Higher doses of fludrocortisone can result in fluid overload and congestive heart failure severe supine hypertension and hypokalaemia. To prevent hypokalaemia food rich in potassium such as fruits vegetables poultry fish and meat is advisable. Headache may occur especially while supine.

Midodrine

Level A Recommendations

Midodrine is recommended for mono- or combined therapy (e.g. with fludrocortisone).
Initial dosage is 2.5 mg orally two to three times daily increasing gradually up to 10 mg t.i.d.
Supine hypertension is a common (25%) adverse effect and may be severe. The last dose should be administered at least 4 hours before going to sleep and BP should be monitored.
Adverse effects are piloerection (goose bumps 13%) scalp or general pruritus (10% and 2%) scalp or general paraesthesia (9% each) urinary retention (6%) and chills (5%).

Some patients worsen on midodrine maybe due to adrenoceptor desensitization. It should be administered with caution in patients with hepatic dysfunction and is contraindicated in severe heart disease acute renal failure urinary retention phaeochromocytoma and thyrotoxicosis.

Dihydroxyphenylserine (DOPS)

Level A Recommendations

In a dosage between 200 and 400 mg per day L-DOPS reduces OH. It is the only effective treatment of dopamine beta-hydroxylase deficiency. In all studies reviewed no major side effects were reported. Future studies will have to investigate which patient groups benefit most from this drug.

Octreotide

Level C Recommendations

Subcutaneous doses of 25 to 50 micrograms half an hour before a meal may be used to reduce post-prandial OH. It does not increase supine hypertension. Nausea and abdominal cramps may occur.

Other Treatment Options

For the drugs listed below there is no clear evidence for use in OH. Many are recommended as GPP and warrant future studies.

Ephedrine that acts on alpha- and beta-adrenergic receptors is recommended by the authors as it reduces OH in many patients particularly with central lesions like MSA (15 mg t.i.d.). Yohimbine an alpha-2-adrenoceptor antagonist with central and peripheral effects has been used in refractory OH (6 mg daily) (class III). Dihydroergotamine (DHE) a direct alpha-adrenoceptor agonist stimulating constriction of venous capacity vessels has shown some benefit and may be used in severe OH (3 to 5 mg t.i.d. oral) (level C class III class III class IV). Desmopressin a vasopressin analogue acts on renal tubular vasopressin-2 receptors diminishing nocturnal polyuria and may be applied as nasal spray (10 to 40 micrograms) or orally (100 to 400 micrograms) at night (class IV). Erythropoietin is recommended in anaemic patients. Indomethacin a prostaglandin synthetase inhibitor has been used in severe OH (75 to 150 mg/day) (class IV class III).

Summary

OH is defined as fall in BP within 3 minutes of active standing or head-up tilt.
The key to managing OH is individually tailored therapy. The goal of treatment is to improve the patient's functional capacity and quality of life preventing injury rather than to achieve a target BP.
Management of patients with OH consists of education advice and training on various factors that influence blood pressure and special aspects that have to be avoided (foods habits positions and drugs).
Physical measures include leg crossing squatting elastic abdominal binders and stockings and careful exercise (GPP).
Increased water (2 to 2.5 l/day) and salt ingestion (>8 g or 150 mmol/day) effectively improve OH.
Fludrocortisone is a valuable starter drug (0.1 to 0.2 mg day level C). Second line drugs include sympathomimetics such as midodrine (start with 2.5 mg twice daily (b.i.d.) and increase to 10 mg t.i.d. level A) or ephedrine (15 mg t.i.d. GPP). DOPS (200 to 400 mg daily level A) reduces OH with only minor side effects. It is an effective treatment in dopamine beta-hydroxylase deficiency.
Supine hypertension has to be considered.
Individual testing with a series of drugs based on the risk of side effects pharmacological interactions and probability of response in the individual patient may be considered when the measures shown here should not be satisfactory.

Definitions:

Evidence Classification Scheme for a Diagnostic Measure

Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum and where test is applied in a blinded evaluation

Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)

Evidence Classification Scheme for a Therapeutic Intervention

Randomization concealment
Primary outcome(s) is/are clearly defined
Exclusion/inclusion criteria are clearly defined
Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences