What are the possible causes and management options for hiccups?

Hiccups: Causes and Management

Overview

For intractable hiccups, chlorpromazine 25-50 mg three to four times daily is the FDA-approved first-line pharmacological treatment, while gastroesophageal reflux disease (GERD) is the most common underlying cause requiring proton pump inhibitor (PPI) therapy. 1, 2

Causes of Hiccups

Pathophysiology

Hiccups result from disruption of a complex reflex arc involving peripheral receptors (phrenic, vagal, and sympathetic pathways) and central brainstem modulation. 3 Any irritant—physical, chemical, inflammatory, or neoplastic—along this arc can trigger hiccups. 3

Classification by Duration

• Acute hiccups: Self-limited, resolve spontaneously (most common)
• Persistent hiccups: Episodes lasting >48 hours 3
• Intractable hiccups: Episodes lasting >2 months 3

Common Etiologies

Peripheral Causes:

• Gastrointestinal (most common): GERD, gastric/duodenal ulcers, gastritis, esophagitis 2, 4
• Cardiac: Myocardial infarction, pericarditis 3, 4
• Thoracic: Tumors, herpes infection 3
• Diaphragmatic irritation: Gastric distention, abdominal surgery 3, 4

Central Causes:

• Stroke, brain tumors, space-occupying lesions 3, 4
• Central nervous system injury 3

Metabolic/Systemic:

• Renal failure 4
• Medications: Anti-parkinsonian drugs, anesthetic agents, steroids, chemotherapy 3
• Alcohol intake 4

Critical Pitfall: Persistent hiccups should be considered a sign of underlying pathology requiring investigation, not merely a benign nuisance. 2

Management Approach

Step 1: Non-Pharmacological Interventions (Acute Hiccups)

Physical Maneuvers:

• Measures that stimulate the uvula/pharynx or disrupt diaphragmatic rhythm 5
• Breath-holding techniques 6
• Larson's maneuver: Apply pressure between the posterior border of the mandible and mastoid process (similar to technique used for laryngospasm) 7

These simple interventions often terminate benign, self-limited hiccup episodes. 5

Step 2: Identify and Treat Underlying Cause (Persistent Hiccups)

Initial Diagnostic Approach:

• First-line empiric therapy: Proton pump inhibitor (PPI) trial, as GERD is the most common cause 2
• Upper gastrointestinal investigations should be performed systematically: endoscopy, pH monitoring, and manometry 4
• If symptoms persist despite PPI therapy, explore central causes with appropriate imaging (brain CT/MRI, chest imaging, abdominal ultrasound) 4

Step 3: Pharmacological Treatment (Intractable Hiccups)

FDA-Approved First-Line Agent:

• Chlorpromazine: 25-50 mg three to four times daily orally 1
• If symptoms persist for 2-3 days on oral therapy, parenteral administration may be indicated 1
• This is the only FDA-approved medication specifically for intractable hiccups 1

Alternative Pharmacological Options Based on Etiology:

For Peripheral Causes:

• Metoclopramide: Recommended as first choice for peripheral causes 6, 4
• Prokinetic agents 3

For Central Causes:

• Baclofen: Drug of choice for central causes of persistent hiccups 6, 4
• Has emerged as a safe and often effective treatment 4

Other Agents with Evidence:

• Gabapentin 3
• Serotonergic agonists 3
• Lidocaine 3

Special Populations:

• Palliative care/terminal illness: Midazolam may be useful 6
• Anesthesia-related: Propofol 1-2 mg/kg IV may be effective 7

Step 4: Interventional Procedures (Refractory Cases)

When medications fail, consider:

• Vagal nerve block or stimulation 6
• Phrenic nerve block or pacing 3, 6
• Acupuncture 3

These interventions should be considered in patients refractory to pharmacological management. 6

Clinical Algorithm Summary

1. Acute hiccups (<48 hours): Physical maneuvers (breath-holding, Larson's maneuver) 7, 5
2. Persistent hiccups (>48 hours): Start PPI empirically + investigate for GERD 2, 4
3. If PPI fails: Investigate other causes (imaging, labs) 4
4. Intractable hiccups:
   • Peripheral causes: Metoclopramide or chlorpromazine 6, 4
   • Central causes: Baclofen 6, 4
   • Unknown/mixed: Chlorpromazine 25-50 mg TID-QID (FDA-approved) 1
5. Refractory to medications: Nerve block/stimulation procedures 6

Important Caveats

• Nearly 4,000 patients are hospitalized annually in the US for hiccups, indicating this is not always a benign condition 2
• The evidence base relies heavily on anecdotal experience rather than controlled trials 5
• Persistent hiccups can cause depression, weight loss, and sleep deprivation, significantly impacting quality of life 4, 6
• Multinational randomized controlled trials are needed to better evaluate treatment strategies 6