What is the functional medicine protocol for dysautonomia (Dysautonomic Syndrome)?

Functional Medicine Protocol for Dysautonomia

For dysautonomia, begin with aggressive non-pharmacological interventions including 2-3 liters of fluid daily, 6-9g salt intake, compression garments, and physical counterpressure maneuvers, then escalate to midodrine (5-20mg three times daily) or fludrocortisone (0.1-0.3mg daily) as first-line pharmacological agents if symptoms persist. 1

Initial Assessment and Diagnosis

Evaluate for specific dysautonomia subtypes through targeted testing:

• Perform a 10-minute stand test measuring heart rate and blood pressure changes from supine to standing 2, 3
• POTS diagnosis requires sustained heart rate increase ≥30 bpm in adults (≥40 bpm in teenagers) or heart rate ≥120 bpm within 10 minutes of standing, without orthostatic hypotension 2, 4
• Neurogenic orthostatic hypotension is defined by sustained systolic blood pressure drop ≥20 mmHg or diastolic drop ≥10 mmHg within 3 minutes of standing 1, 2
• Screen for underlying causes including diabetes, autoimmune disorders, vitamin deficiencies, Ehlers-Danlos syndrome, and medication effects (diuretics, vasodilators, tricyclic antidepressants) 5, 3
• Assess for comorbidities such as mast cell activation syndrome, gastrointestinal dysmotility, chronic fatigue, and joint hypermobility 5, 6

Non-Pharmacological Interventions (First-Line Treatment)

Fluid and Salt Management

• Increase fluid intake to 2-3 liters daily unless contraindicated by cardiac or renal disease 5, 1
• Increase salt consumption to 6-9g daily through dietary sources or salt tablets 5, 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Postural and Physical Measures

• Elevate head of bed 10-30 degrees during sleep to prevent nocturnal polyuria and reduce supine hypertension 5, 1
• Use compression garments including thigh-high stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 5, 1, 4
• Implement physical counterpressure maneuvers such as leg crossing, muscle tensing, and squatting when prodromal symptoms occur 5, 1
• Avoid trigger factors including hot environments, prolonged standing, dehydration, and large carbohydrate-heavy meals 5, 1

Dietary Modifications

• Consume smaller, more frequent meals with reduced carbohydrate content to minimize postprandial hypotension 5, 1
• Maintain adequate hydration with electrolyte-containing beverages ("sport drinks") 5

Exercise and Reconditioning

• Initiate supervised exercise training focusing on recumbent activities (sitting, lying, or water-based exercise) to avoid deconditioning 5, 4
• Avoid graded exercise therapy in patients with postexertional malaise or chronic fatigue syndrome, as 75% of patients worsen with physical activity 5
• Consider tilt-training protocols in highly motivated patients with recurrent vasovagal symptoms 5

Pharmacological Interventions (Second-Line Treatment)

First-Line Medications

Midodrine (Alpha-1 Agonist)

• Dosing: 5-20mg three times daily, with last dose before 6 PM to avoid supine hypertension 1, 7
• Mechanism: Increases vascular tone through alpha-adrenergic receptor activation, elevating standing systolic blood pressure by 15-30 mmHg at 1 hour post-dose 7
• Indications: Neurogenic orthostatic hypotension (Class IIa, Level B-R) and recurrent vasovagal syncope with orthostatic component 1, 4
• Peak effect: 1-2 hours after administration with duration of 2-3 hours 7

Fludrocortisone (Mineralocorticoid)

• Dosing: 0.1-0.3mg once daily 5, 1, 4
• Mechanism: Promotes sodium retention and plasma volume expansion 5
• Indications: Neurogenic orthostatic hypotension (Class IIa, Level C-LD) and vasovagal syncope with inadequate response to salt/fluid intake (Class IIb, Level B-R) 1
• Monitor: Electrolyte abnormalities, particularly hypokalemia 1

Alternative Pharmacological Options

Beta-Blockers

• Pyridostigmine may be considered for POTS management 5, 4
• Avoid beta-blockers in vasovagal syncope as they lack efficacy and may worsen cardioinhibitory bradycardia (Class III recommendation) 5, 1

Droxidopa

• Reserved for refractory neurogenic orthostatic hypotension (Class IIa, Level B-R) 1
• Note: Not available in Brazil 2

Ivabradine

• May be used for heart rate control in select POTS patients 3

Medications to Discontinue

• Review and reduce or eliminate diuretics, vasodilators, nitrates, tricyclic antidepressants, and antiparkinsonian medications that worsen hypotension 5, 1
• Avoid opioids as they suppress immune function, increase infection risk, and worsen gastrointestinal dysmotility 5

Management of Supine Hypertension

Critical consideration: Over 50% of neurogenic orthostatic hypotension patients develop supine hypertension 2

• Prioritize orthostatic hypotension treatment over supine hypertension, as immediate risks of falls and syncope outweigh long-term hypertension risks 5, 1, 2
• Tolerate supine blood pressure up to 160/90 mmHg 2
• For severe supine hypertension, use short-acting antihypertensives at bedtime: losartan, captopril, clonidine, or nitrate patches 2
• Maintain head-of-bed elevation to reduce nocturnal hypertension 5, 1
• Avoid nighttime standing to prevent triggering hypotensive episodes 2

Treatment of Comorbid Conditions

Gastrointestinal Symptoms

• Nausea/vomiting: Ondansetron, promethazine, prochlorperazine, metoclopramide, or domperidone 5
• Constipation: Osmotic/stimulant laxatives, lubiprostone, linaclotide, plecanatide, or prucalopride 5
• Diarrhea: Loperamide, bile acid sequestrants (cholestyramine, colestipol), or ondansetron 5
• Abdominal pain: Antispasmodics (hyoscyamine, dicyclomine, peppermint oil) or neuromodulators (tricyclic antidepressants, SSRIs, SNRIs, pregabalin, gabapentin) 5
• Bacterial overgrowth: Rotating antibiotics (rifaximin, ciprofloxacin, metronidazole) at lowest effective doses 5

Mast Cell Activation Syndrome

• H1 and H2 antihistamines (particularly famotidine) for symptom relief 5
• Consider low-dose naltrexone for pain, fatigue, and neurological symptoms 5

Chronic Fatigue and Postexertional Malaise

• Implement pacing strategies for both physical and cognitive activities 5
• Consider coenzyme Q10 and D-ribose supplementation 5
• Avoid exercise as treatment in patients with postexertional malaise 5

Device-Based Interventions

Cardiac Pacing

• Consider permanent dual-chamber pacing for carotid sinus syndrome with cardioinhibitory or mixed pattern (Class IIa, Level B-R) 1
• Not indicated for vasovagal syncope without documented cardioinhibitory reflex, as pacing fails to prevent syncope 5, 1

Monitoring and Follow-Up

• Regular assessment for adverse effects, particularly supine hypertension with pressor agents and electrolyte abnormalities with fludrocortisone 1
• Reassess medication regimen periodically as dysautonomia may reveal subclinical dysfunction 2
• Monitor nutritional status including BMI, weight changes, and micronutrient deficiencies (iron, vitamin B12, fat-soluble vitamins, magnesium) 5
• Screen for bone density loss with DEXA scanning in malnourished patients 5

Special Populations

Elderly Patients

• Recognize atypical presentations including absence of premonitory symptoms and complete amnesia in up to 40% of cases 5
• Address polypharmacy as a primary contributor to orthostatic intolerance 5

Diabetic Patients

• Optimize glycemic control as 38-44% develop dysautonomia with poor control 2
• Recognize progression pattern: parasympathetic dysfunction first, then sympathetic, finally orthostatic hypotension 2

Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorders

• Evaluate for pelvic floor dysfunction with anorectal manometry in patients with incomplete evacuation 5
• Consider earlier gastric emptying studies in patients with POTS and upper GI symptoms 5
• Screen for celiac disease in patients with varied GI symptoms, not just diarrhea 5