What is the management of hiccups?

Management of Hiccups

For intractable hiccups, chlorpromazine 25-50 mg three to four times daily is the FDA-approved first-line pharmacological treatment, while persistent hiccups should initially be treated with high-dose proton pump inhibitor (PPI) therapy when gastroesophageal reflux disease (GERD) is suspected. 1, 2

Definition and Classification

Hiccups are sudden, involuntary contractions of the diaphragm and intercostal muscles immediately followed by laryngeal closure, producing the characteristic "hic" sound. 3 The classification system divides hiccups into:

• Acute hiccups: Episodes lasting less than 48 hours 4
• Persistent hiccups: Episodes lasting 48 hours to 2 months 3
• Intractable hiccups: Episodes lasting longer than 2 months 3

Pathophysiology and Mechanism

The hiccup reflex arc involves peripheral phrenic, vagal, and sympathetic pathways with central midbrain modulation. 3 Any physical, chemical, inflammatory, or neoplastic irritant along this arc can trigger hiccups. 3 The reflex involves:

• Peripheral receptors: Phrenic nerve, vagus nerve, and sympathetic chain (T6-T12) 3
• Central processing: Brainstem hiccup center with supraspinal modulation 5, 3
• Effector pathway: Phrenic nerve stimulation causing diaphragmatic contraction 3

Clinical Significance and Complications

Untreated persistent hiccups can lead to weight loss, depression, and sleep deprivation. 2, 6 Approximately 4,000 patients are admitted to hospitals in the United States annually for hiccups. 7

Investigations

Initial Evaluation

When hiccups persist beyond 48 hours, investigate for underlying pathology with the following approach: 6, 4

• Gastrointestinal causes (most common): Look for gastric distention, GERD, gastritis, peptic ulcer disease, esophagitis 6, 7, 4
• Cardiovascular causes: Myocardial infarction, pericardial effusion compressing the phrenic nerve (presenting with local compression symptoms) 2, 6
• Central nervous system causes: Brain tumors, traumatic brain injury, stroke, space-occupying lesions 2, 3
• Thoracic causes: Evaluate with chest X-ray if pericardial or thoracic pathology suspected 2

Diagnostic Testing Algorithm

1. Upper gastrointestinal investigations should be included systematically: Endoscopy, pH monitoring, and manometry 6
2. Imaging studies: Chest X-ray and echocardiography if pericardial effusion suspected; abdominal ultrasound; brain CT scan for central causes 2, 6
3. Consider 24-hour esophageal pH monitoring if empiric PPI therapy is unsuccessful 2

Management

Acute Hiccups (< 48 hours)

Physical maneuvers that stimulate the uvula/pharynx or disrupt diaphragmatic rhythm should be attempted first, as acute hiccups rarely require medical intervention. 5, 4 These include:

• Breath-holding techniques 3
• Pharyngeal stimulation 5
• Measures to disrupt respiratory rhythm 5

Persistent Hiccups (48 hours to 2 months)

Initiate high-dose PPI therapy as first-line treatment when GERD is the suspected cause, with response time variable from 2 weeks to several months. 2 The treatment algorithm is:

1. Start high-dose PPI therapy immediately 2
2. Implement antireflux diet and lifestyle modifications concurrently 2
3. Add prokinetic therapy (such as metoclopramide) if partial or no improvement occurs 2
4. Consider 24-hour esophageal pH monitoring if empiric therapy unsuccessful 2

Intractable Hiccups (> 2 months)

Chlorpromazine is the FDA-approved first-line pharmacological agent for intractable hiccups. 1 The dosing regimen is:

• Initial dose: 25-50 mg three to four times daily orally 1
• If symptoms persist for 2-3 days: Switch to parenteral therapy 1
• Maximum benefit: May require several weeks; maintenance therapy may be necessary 1

Important safety considerations with chlorpromazine: Can cause hypotension, sedation, extrapyramidal symptoms, and QT interval prolongation. 2 Elderly patients are more susceptible to hypotension and neuromuscular reactions and should be observed closely with lower initial doses. 1

Alternative Pharmacological Agents

When chlorpromazine is contraindicated or ineffective:

• Metoclopramide: Recommended as a second-line agent by oncology guidelines and as an alternative treatment option 2, 5, 6
• Baclofen: Has emerged as a safe and often effective treatment 6
• Gabapentin: Alternative pharmacological option 3

Non-Pharmacological Interventions

For refractory cases:

• Nerve blockade: Phrenic nerve disruption 5, 3
• Acupuncture: May be beneficial in severe cases 5, 3
• Hypnosis: Used in intractable cases 5

Critical Pitfalls to Avoid

• Do not dismiss persistent hiccups as benign: They may indicate serious underlying pathology including myocardial infarction, brain tumor, renal failure, or malignancy 6, 4
• Do not delay gastrointestinal evaluation: GERD and related conditions are the most common identifiable causes and should be investigated systematically 6, 7
• Do not overlook pericardial effusion: Hiccups with other local compression symptoms warrant immediate imaging with chest X-ray and echocardiography 2
• Do not use chlorpromazine without monitoring: Watch for hypotension, especially in elderly patients, and monitor QT interval 2, 1