What causes hiccups?

Causes of Hiccups

Hiccups result from disruption anywhere along a complex reflex arc involving peripheral receptors (phrenic, vagus, and sympathetic nerves) and central brainstem modulation, with gastroesophageal reflux disease (GERD) being the most common pathological cause. 1, 2

Pathophysiology

Hiccups are sudden, involuntary contractions of the diaphragm and intercostal muscles immediately followed by glottic closure, producing the characteristic "hic" sound. 2, 3 The reflex arc consists of:

• Peripheral afferent limbs: Phrenic nerve, vagus nerve, and sympathetic pathways (T6-T12) 2, 4
• Central processing: Hiccup center located in the brainstem 2, 3
• Efferent pathway: Primarily the phrenic nerve to the diaphragm 2

Any irritant—physical, chemical, inflammatory, or neoplastic—affecting this arc can trigger hiccups. 2

Major Categories of Causes

Gastrointestinal Causes (Most Common)

• GERD is the most common pathological cause and should be the primary consideration in persistent hiccups 1, 5
• Gastric distention (the most common trigger for benign, self-limited hiccups) 5
• Gastric and duodenal ulcers, gastritis, esophagitis 5
• Abdominal surgery 5

Clinical Pearl: Upper gastrointestinal investigations including endoscopy, pH monitoring, and manometry should be included systematically in the diagnostic evaluation of chronic hiccups. 5

Central Nervous System Causes

• Stroke 2, 5
• Space-occupying lesions and brain tumors 2, 5
• CNS injury 2

Cardiovascular Causes

• Myocardial ischemia and infarction 2, 5
• Pericarditis and pericardial effusion (via phrenic nerve compression) 6

Peripheral Nerve Irritation

• Tumors along the reflex arc 2
• Herpes infection 2
• Applied instrumentation on the body 2

Metabolic and Systemic

• Renal failure 5
• Metabolic/endocrine disorders 3
• Infections 3

Drug-Induced Hiccups

• Anti-Parkinsonian drugs 2
• Anesthetic agents 2
• Steroids and chemotherapy agents 2
• Aripiprazole (acts as dopamine agonist at low doses <7.5 mg/day, stimulating D2/D3 receptors at the hiccup center) 3

Other Causes

• Alcohol intake 5
• ENT conditions 3
• Pneumological problems 3
• Psychogenic disorders 3

Clinical Classification by Duration

• Acute/benign: Self-limited, resolve spontaneously 2, 5
• Persistent: Episodes lasting >48 hours 2
• Intractable: Episodes lasting >2 months 2

Important Clinical Considerations

When hiccups persist beyond 48 hours, they should be considered a sign of underlying pathology requiring investigation. 1 Prolonged hiccups can cause significant morbidity including depression, weight loss, and sleep deprivation. 5

Common Pitfall: Failing to recognize that persistent hiccups warrant a thorough diagnostic workup rather than symptomatic treatment alone. The underlying cause must be identified and treated when possible. 1, 5

Initial Diagnostic Approach

For persistent hiccups, first-line therapy should involve:

• Proton pump inhibitor (PPI) trial (given GERD is the most common cause) 1
• Appropriate gastrointestinal consultation 1
• If symptoms persist despite PPI therapy, investigate central and other peripheral causes 1

Detailed medical history and physical examination will guide diagnostic investigations including abdominal ultrasound, chest or brain CT scan as clinically indicated. 5