What are the causes of hiccups?

Causes of Hiccups

Overview and Mechanism

Hiccups result from involuntary spasmodic contractions of the diaphragm and intercostal muscles followed by abrupt glottic closure, producing the characteristic "hic" sound. 1, 2 The underlying mechanism involves a reflex arc with both peripheral (phrenic nerve, vagus nerve, and sympathetic pathways) and central (midbrain) components. 3 Any irritant—physical, chemical, inflammatory, or neoplastic—affecting this reflex arc can trigger hiccups. 3

Central Nervous System Causes

The brain and spinal cord can directly trigger hiccups through several mechanisms:

• Brain tumors are a recognized cause of persistent hiccups. 4
• Traumatic brain injury can initiate the hiccup reflex through central pathway disruption. 4
• Stroke and space-occupying lesions affecting the midbrain modulation centers are important central causes. 3
• Inflammatory disorders of the central nervous system, including meningitis, can trigger the reflex. 5, 3

Peripheral Nerve Irritation

Phrenic Nerve Pathway

• Pericardial effusion compressing the phrenic nerve causes hiccups as a local compression symptom. 4
• Proliferative disorders and goiter can irritate the phrenic nerve directly. 5
• Chest injury or thoracic surgery may mechanically stimulate phrenic nerve pathways. 5

Vagus Nerve Pathway

The vagus nerve is the most common peripheral pathway involved:

• Gastroesophageal reflux disease (GERD) is the single most important gastrointestinal cause of hiccups. 2
• Myocardial ischemia and infarction can present with hiccups as a secondary symptom through vagal irritation. 5
• Esophageal, gastric, and duodenal diseases trigger hiccups via vagal afferents. 5
• Hepatitis, pancreatitis, and enteritis stimulate the vagal pathway. 5
• Otolaryngologic diseases affecting ear, nose, and throat structures can activate vagal fibers. 5

Respiratory and Thoracic Causes

• Pneumonias, including COVID-19, have been reported to trigger persistent hiccups even without obvious respiratory symptoms. 1
• Chest wall disorders from trauma or surgical manipulation can initiate the reflex. 5

Pharmacologic Causes

Multiple medication classes can induce hiccups:

• Anti-Parkinsonian drugs are recognized triggers. 3
• Anesthetic agents during or after procedures. 3
• Steroids and chemotherapy agents are common culprits in oncology patients. 3

Metabolic and Systemic Causes

• Metabolic disorders affecting the central nervous system can trigger hiccups through disruption of the hiccup center. 5
• Psychogenic factors may stimulate the central hiccup mechanism. 5

Clinical Significance and Red Flags

Hiccups persisting beyond 48 hours should raise suspicion for an underlying pathologic cause requiring investigation. 1, 2 The distinction between benign self-limited hiccups and pathologic persistent hiccups is critical:

• Acute hiccups (< 48 hours) are usually physiologic and self-limited. 2
• Persistent hiccups (> 48 hours) warrant diagnostic evaluation. 1, 2
• Intractable hiccups (> 2 months) require comprehensive workup and aggressive management. 6, 3

Consequences of Untreated Persistent Hiccups

When hiccups become pathologic, they significantly impact patient outcomes:

• Weight loss occurs from inability to eat normally. 4
• Depression develops from the chronic, stigmatizing nature of the condition. 4, 6
• Significant fatigue and insomnia result from persistent episodes. 5
• Alkalosis may develop in tracheotomized patients due to hyperventilation. 2

Diagnostic Approach

When evaluating persistent hiccups, prioritize investigation based on the reflex arc:

• Imaging studies including chest X-ray and echocardiography are recommended when pericardial or thoracic pathology is suspected. 4
• Initiate high-dose PPI therapy empirically when GERD is suspected, with response time variable from 2 weeks to several months. 4
• Consider 24-hour esophageal pH monitoring if empiric GERD therapy is unsuccessful. 4
• Thorough history and physical examination should focus on identifying lesions along the hiccup reflex arc, including cardiac symptoms (exertional hiccups may indicate ischemia), neurologic deficits, and gastrointestinal symptoms. 1, 5