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Circulation. 2017;136:e60–e122. DOI: 10.1161/CIR.0000000000000499 August 1, 2017 e87 CLINICAL STATEMENTS AND GUIDELINES

Recommendations for Neurogenic OH

COR LOE Recommendations

I B-R Acute water ingestion is recommended in patients with syncope caused by neurogenic OH for occasional, temporary relief.438,439

See Online Data Supplements 33–35. In neurogenic OH, acute water ingestion can temporarily restore orthostatic tolerance.438–444 The pressor effect of water is most likely sympathetically driven, with the peak effect occurring 30 minutes after ingestion of ≥240 mL and additional benefit seen with ≥480 mL.398,441,442 The presence of glucose or salt may reduce this effect by splanchnic vasodilatation or a decreased osmopressor response, respectively.397,439 Acute water ingestion for temporary relief of OH is not intended for routine or long-term use.24

IIa C-LD Physical counter-pressure maneuvers can be beneficial in patients with neurogenic OH with syncope.374,445–450

See Online Data Supplements 33–35. Isometric contraction, such as by leg crossing, lower body muscle tensing, and maximal force handgrip, can increase blood pressure, with the largest effect occurring with squatting versus other counter-pressure maneuvers.374,445–450 Leg crossing increases cardiac output in patients with neurogenic hypotension.447 Similar or larger benefit would be expected with squatting and other isometric contraction.449 The benefit is limited to patients with sufficient prodrome and the ability to perform these maneuvers adequately and safely.449

IIa C-LD Compression garments can be beneficial in patients with syncope and OH.451–455

See Online Data Supplements 33–35. In patients with OH, including older adult patients and those with neurogenic etiologies, compression garments can improve orthostatic symptoms and blunt associated decreases in blood pressure.451–456 The garments should be at least thigh high and preferably include the abdomen, as shorter garments have not been proved to be beneficial.457

IIa B-R Midodrine can be beneficial in patients with syncope due to neurogenic OH.458–467

See Online Data Supplements 33–35. Midodrine improves symptoms of OH in patients with neurogenic OH.458–467 There is a dose-dependent effect, usually corresponding to an increase in standing blood pressure.459,460,462,463,466,467 Its use may be limited by supine hypertension, and other common side effects include scalp tingling, piloerection, and urinary retention.459,460,463,467

IIa B-R Droxidopa can be beneficial in patients with syncope due to neurogenic OH.380,468–471

See Online Data Supplements 33–35. Droxidopa improves symptoms of neurogenic OH due to Parkinson disease, pure autonomic failure, and multiple system atrophy.380,468,470,471 Droxidopa might reduce falls, according to small studies.472 Use of carbidopa in patients with Parkinson disease may decrease the effectiveness of droxidopa.380 Use and titration of droxidopa may be limited by supine hypertension,380,469 headache, dizziness, and nausea.468,470–472

IIa C-LD Fludrocortisone can be beneficial in patients with syncope due to neurogenic OH.473–476

See Online Data Supplements 33–35. Fludrocortisone increases plasma volume, with a resultant improvement in symptoms of OH.473,477,478 When taken regularly, fludrocortisone may prevent OH, at least in astronauts after space flight.476 Supine hypertension may be a limiting factor. When supine hypertension is present, other medications should be used before fludrocortisone. Other side effects commonly seen include edema, hypokalemia, and headache, but more serious adverse reactions, such as adrenal suppression and immunosuppression, can also occur with doses >0.3 mg daily.479,480

IIb C-LD Encouraging increased salt and fluid intake may be reasonable in selected patients with neurogenic OH.396,398,441,443,444

See Online Data Supplements 33–35. Although the data are limited for salt and fluid supplementation in patients with OH, these 2 treatments may improve blood pressure while decreasing symptoms from OH.396,398,439–444 Salt supplementation (eg, 6 to 9 g [100 to 150 mmol; about 1 to 2 teaspoons] of salt per day) increases plasma volume, with limited benefit in patients with already high salt intake.396 Water ingestion increases the blood pressure via a pressor effect, most likely mediated by sympathetic activation, with a peak effect approximately 30 minutes after ingestion.398,439,441–443 This additional salt and fluid intake may not be beneficial in patients with history of hypertension, renal disease, HF, or cardiac dysfunction, and the long-term effects of these treatments, including the benefits and risks, is unknown.

IIb C-LD Pyridostigmine may be beneficial in patients with syncope due to neurogenic OH who are refractory to other treatments.466,481,482

See Online Data Supplements 33–35. In patients with autonomic failure and neurogenic OH, pyridostigmine is able to improve orthostatic tolerance through increases in peripheral vascular resistance and blood pressure.481,482 Side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence.483

IIb C-LD Octreotide may be beneficial in patients with syncope and refractory recurrent postprandial or neurogenic OH.484–487

See Online Data Supplements 33–35. Splanchnic circulation pooling can contribute to OH, and this pooling can worsen in the postprandial period.484–487 Octreotide reduces splanchnic blood flow by approximately 20%,486 which prevents postprandial hypotension, increases blood pressure, and improves orthostatic tolerance.484–487

return to the heart drops, with a resultant decrease in cardiac output.31 Normally, the autonomic nervous system provides compensatory changes in vascular tone, heart rate, and cardiac contractility. In some individuals, this response may be defective or inadequate.31 In neurogenic OH, the vasoconstrictor mechanisms of vascular tone may be inadequate because of neurodegenerative disorders, such as multiple system atrophy, pure autonomic failure, Parkinson’s disease, and autonomic peripheral neuropathies, such as those due to diabetes mellitus and other systemic diseases.31 Neurogenic OH may present clinically as classic or delayed OH. Most commonly, OH is due to dehydration or medications, such as diuretics and vasodilators. Syncope caused by OH conditions occurs in the upright position. See Figure 5 for the algorithm for treatment of OH.

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