What are the causes of persistent hiccups?

Causes of Persistent Hiccups

Persistent hiccups result from disruption anywhere along the hiccup reflex arc, which involves peripheral phrenic, vagal, and sympathetic pathways with central midbrain modulation. 1

Gastrointestinal Causes (Most Common)

Gastroesophageal reflux disease (GERD) is the most commonly identifiable cause of persistent hiccups in both adults and children. 2, 3, 4, 5

• Gastric overdistension is the most frequent trigger for acute hiccups that may progress to persistent episodes 5
• Gastritis can precipitate persistent hiccups 5
• Any gastrointestinal pathology irritating the vagal or phrenic nerve pathways may trigger hiccups 1

Central Nervous System Causes

Central causes include any lesion affecting the brainstem hiccup reflex center or its connections. 2, 1

• Brain tumors and space-occupying lesions 2, 1
• Traumatic brain injury 2
• Stroke affecting the midbrain or brainstem 1
• Central nervous system injury 1

Cardiovascular Causes

Pericardial pathology causing phrenic nerve compression is an important cardiovascular etiology. 2, 6

• Pericarditis 6
• Pericardial effusion compressing the phrenic nerve 2, 6
• Myocardial ischemia 1

Peripheral Nerve Irritation

Any lesion along the phrenic or vagal nerve pathways can trigger persistent hiccups. 1

• Tumors compressing or invading the phrenic nerve 1
• Herpes infection affecting nerve pathways 1
• Applied instrumentation on the body irritating nerve pathways 1

Medication-Induced Causes

Multiple drug classes can cause persistent hiccups through various mechanisms. 1

• Anti-parkinsonism drugs 1
• Anesthetic agents 1
• Steroids 1
• Chemotherapy agents 1

Psychogenic Causes

Anxiety disorders and stress can contribute to hiccup generation. 7

• This represents a less common but recognized etiology requiring consideration when organic causes are excluded 7

Clinical Pitfalls

A critical pitfall is dismissing persistent hiccups (>48 hours) as benign when they may indicate serious underlying pathology. 3, 5

• Untreated persistent hiccups can lead to weight loss and depression 2
• Nearly 4,000 patients are hospitalized annually in the US for hiccups, indicating the severity of some cases 3
• The reflex arc complexity means that physical factors, chemical irritants, inflammation, or neoplasia anywhere along the pathway can trigger hiccups 1

When evaluating persistent hiccups, imaging including chest X-ray and echocardiography should be obtained if pericardial or thoracic pathology is suspected. 2