Does vagus nerve dysfunction cause gastroparesis in postural orthostatic tachycardia syndrome, and how is it treated?

Vagus Nerve Dysfunction and Gastroparesis in POTS

Yes, vagus nerve dysfunction is recognized as a mechanism causing gastroparesis in POTS patients, and treatment should target the predominant symptom using a stepwise approach starting with dietary modification, prokinetics for delayed emptying, and neuromodulators for pain—while strictly avoiding opioids. 1

Established Link Between POTS and Gastroparesis

POTS is a form of dysautonomia where autonomic dysfunction can occur at multiple levels including peripheral nerves, autonomic ganglia, spinal cord, and brain, resulting in alimentary tract defects among other organ system impairments. 1 The vagus nerve, as part of the parasympathetic autonomic nervous system, directly innervates the gastrointestinal tract and controls gastric motility. 1

Evidence of Gastroparesis in POTS

The prevalence of gastric emptying abnormalities in POTS patients with GI symptoms is substantial:

• Approximately one-third (34%) of POTS patients with gastrointestinal symptoms have abnormal gastric emptying, though rapid emptying (48%) is actually more common than delayed emptying (18%) in this population. 2
• Nausea and vomiting occur in over 70% of POTS patients with GI symptoms, making these the most common manifestations. 3
• Abdominal pain (59%), bloating (55%), and postprandial fullness/early satiety (46%) are other frequent complaints. 3

Pathophysiological Mechanisms

The connection between POTS and gastroparesis involves multiple mechanisms beyond simple vagal dysfunction:

• The underlying autonomic dysfunction in POTS predisposes to gastroparesis and perturbations in GI motility. 4
• Vagal nerve injury is specifically identified as one of the putative factors involved in generating refractory gastroparesis symptoms. 1
• In neuropathic POTS phenotypes, gastrointestinal tract motility and gut hormonal secretion may be directly impaired due to localized autonomic denervation. 5
• Increased variability of gastric pacemaker rhythm has been demonstrated in POTS patients, particularly those with GI symptoms, suggesting dysregulation of gastric myoelectrical activity. 6

An important caveat: The majority of GI symptoms in POTS patients are not directly caused by orthostatic stress but represent comorbid conditions. 7 Only symptoms that develop in the upright position and resolve when supine are truly related to the orthostatic disorder itself. 7

Diagnostic Approach

When to Test for Gastroparesis

Timely diagnostic testing of gastric motor functions (gastric emptying and/or accommodation) should be considered earlier in POTS patients with chronic upper GI symptoms, as abnormal gastric emptying may be more common than in the general population. 4

The threshold for gastric emptying studies should be lower in POTS patients compared to the general population—do not delay testing. 4

Specific Testing Recommendations

• Gastric emptying scintigraphy of a radiolabeled solid meal performed for up to 4 hours is the best accepted method to diagnose delayed gastric emptying. 1
• Assess for opioid use, as opioids can cause or exacerbate GI dysmotility and must be withdrawn. 4
• Test for celiac disease earlier in the diagnostic workup, as the risk is elevated in POTS patients, even without isolated diarrhea. 4

Treatment Algorithm

Step 1: Dietary Modification (First-Line)

Begin with small particle size, reduced fat, low-fiber diet as the foundation of gastroparesis management. 1

Step 2: Symptom-Targeted Pharmacotherapy

Identify the predominant symptom and initiate treatment based on that specific symptom. 1

For Nausea and Vomiting:

Multiple antiemetic options are available and should be utilized: 1

• Antiemetics: ondansetron, promethazine, prochlorperazine, aprepitant 4
• Prokinetics for documented delayed emptying: metoclopramide (first-line), domperidone, erythromycin, prucalopride 4

For Abdominal Pain:

Use neuromodulators to treat gastroparesis-associated abdominal pain, but strictly avoid opioids. 1

• Neuromodulators: tricyclic antidepressants (TCAs), SSRIs, SNRIs, pregabalin, gabapentin 4
• Acid-suppressive drugs: PPIs, H2 antagonists 4
• Antispasmodics: hyoscyamine, dicyclomine, peppermint oil 4

Critical pitfall: Do not prescribe opioids for pain management, as they worsen GI dysmotility and should be withdrawn if already prescribed. 4

Step 3: Advanced Interventions for Refractory Cases

For patients with refractory/intractable nausea and vomiting who have failed standard therapy and are not on opioids, gastric electrical stimulation (GES) can be considered. 1

For select refractory gastroparesis patients with severe delay in gastric emptying, gastric per-oral endoscopic myotomy (G-POEM) can be considered using a thoughtful team approach involving motility specialists and advanced endoscopists at a center of excellence. 1

Special Considerations in POTS

Overlapping Conditions

Do not attribute all symptoms to POTS alone—systematically evaluate for overlapping conditions like hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS), and disorders of gut-brain interaction (DGBI). 4

• Patients with hEDS/HSDs have a 37.5% prevalence of POTS, and those with concomitant POTS are more likely to have IBS, GERD, or dysmotility. 1
• Visceral hypersensitivity and/or dysmotility are common mechanisms underlying GI symptoms in POTS patients. 4

Autonomic Dysfunction Patterns

The pattern of autonomic dysfunction does not reliably discriminate between patients with normal, rapid, or delayed gastric emptying, except that more severe adrenergic impairment is associated with delayed gastric emptying. 2

Physical Deconditioning

Physical deconditioning is present in 36% of POTS patients and is specifically associated with rapid gastric emptying rather than delayed emptying. 2 This highlights that extravascular volume depletion and deconditioning may contribute to POTS symptoms in patients with GI complaints. 2

Common Pitfalls to Avoid

1. Do not delay gastric emptying studies—test earlier than you would in the general population. 4
2. Do not prescribe or continue opioids, as they directly worsen gastroparesis. 4
3. Do not overlook that rapid gastric emptying is actually more common than delayed emptying in POTS patients. 2
4. Do not assume GI symptoms are solely due to orthostatic stress—most represent comorbid functional GI disorders. 7
5. Do not miss evaluation for pelvic floor dysfunction if constipation or incomplete evacuation is present. 4