What are the causes of intractable hiccups?

Causes of Intractable Hiccups

Intractable hiccups are most commonly caused by neurological disorders affecting the brainstem, particularly lesions in the area postrema of the medulla, and should be thoroughly investigated for underlying pathologies that may significantly impact mortality and morbidity. 1

Neurological Causes

Central Nervous System

• Brainstem lesions:
  • Area postrema lesions (particularly in neuromyelitis optica spectrum disorders) 1
  • Periaqueductal lesions 1
  • Medullary lesions (may be contiguous with cervical cord lesions) 1
• Stroke (especially cerebellar infarction) 1
• Space-occupying lesions (tumors, abscesses) 2
• Multiple sclerosis (particularly with infratentorial lesions) 1

Gastrointestinal Causes

• Gastroesophageal reflux disease (GERD) - often underestimated as a cause 3
• Esophagitis 3
• Distention of the stomach 2
• Hepatomegaly or other conditions causing diaphragmatic irritation 2

Thoracic/Diaphragmatic Causes

• Diaphragmatic eventration - structural abnormality of the diaphragm 4
• Myocardial ischemia - can irritate the phrenic nerve 2
• Pericarditis 2
• Thoracic tumors (especially those involving the phrenic nerve) 2

Infectious/Inflammatory Causes

• Herpes zoster (affecting thoracic dermatomes) 2
• CNS infections (encephalitis, meningitis) 2
• Neuro-Behçet disease (associated with large diencephalic and infratentorial lesions) 1

Autoimmune Causes

• Neuromyelitis optica spectrum disorders - characterized by area postrema syndrome with intractable hiccups and vomiting 1
• Anti-MOG syndrome - can present with brainstem lesions 1

Metabolic/Toxic Causes

• Uremia 2
• Medications:
  • Anti-Parkinsonism drugs 2
  • Anesthetic agents 2
  • Steroids 2
  • Chemotherapeutic agents 2

Structural/Mechanical Causes

• Oral-pharyngeal dysphagia - can be associated with intractable hiccups 1
• Foreign bodies irritating the vagus or phrenic nerves 2

Post-procedural Causes

• Post-surgical (especially after thoracic or abdominal procedures) 2
• Instrumentation (endoscopy, intubation) 2

Diagnostic Approach

When evaluating intractable hiccups, consider:

1. Brain and spine MRI - essential to identify central lesions, particularly in the brainstem and area postrema 1
2. Upper endoscopy - to evaluate for GERD and esophagitis 3
3. Chest imaging - to identify thoracic causes including diaphragmatic abnormalities 4
4. Laboratory tests - to rule out metabolic causes 2

Treatment Considerations

For pharmacological management:

• Chlorpromazine (25-50 mg three to four times daily) - FDA-approved for intractable hiccups 5
• Metoclopramide (5-10 mg four times daily) - particularly effective when GERD is suspected 6
• Baclofen and gabapentin - alternative options for neurological causes 7

Important Pitfalls to Avoid

1. Missing neuromyelitis optica spectrum disorders - intractable hiccups with area postrema lesions are a classic presentation and require specific treatment 1
2. Overlooking GERD - often underdiagnosed as a cause of persistent hiccups 3
3. Focusing only on symptomatic treatment without identifying the underlying cause can lead to delayed diagnosis of serious conditions 2
4. Assuming benign etiology - intractable hiccups (lasting >48 hours) warrant thorough investigation as they often indicate serious underlying pathology 2

Remember that intractable hiccups in cerebellar stroke can precede deterioration in consciousness and may be an early warning sign of impending brainstem compression requiring urgent intervention 1.