Treatment of Intractable Hiccups
For intractable hiccups, chlorpromazine 25-50 mg orally three to four times daily is the first-line pharmacological treatment, as it remains the only FDA-approved medication for this indication. 1
Initial Management Approach
Non-Pharmacological Interventions
- Physical maneuvers should be attempted first for acute hiccups, including applying pressure between the posterior border of the mandible and mastoid process (similar to Larson's maneuver). 2
- These maneuvers work by overstimulating the vagus nerve and may terminate hiccups without medication. 3
When to Escalate to Pharmacotherapy
- If hiccups persist for 2-3 days despite physical maneuvers, initiate pharmacological therapy. 1
- Monitor patients approaching 48 hours for signs of respiratory compromise, especially those with pre-existing conditions. 4
Pharmacological Treatment Algorithm
First-Line: Chlorpromazine (FDA-Approved)
- Dosing: 25-50 mg orally three to four times daily 1
- If oral therapy fails after 2-3 days: Switch to intramuscular route (25-50 mg IM) 5
- For severe refractory cases: Slow IV infusion of 25-50 mg in 500-1000 mL saline with patient flat in bed, monitoring blood pressure closely 5
- Critical warnings: Can cause hypotension, sedation, extrapyramidal symptoms, and QT prolongation 6
- Evidence base: Supported by observational data and systematic reviews as effective treatment 7
Second-Line: Metoclopramide
- Recommended as a second-line agent by multiple guidelines when chlorpromazine fails or is contraindicated 8, 6
- Dosing: 10-20 mg orally or IV every 4-6 hours 8
- Alternative dosing for gastroparesis-related hiccups: 5-10 mg orally four times daily, 30 minutes before meals and at bedtime 8
- Evidence base: Supported by small randomized controlled trials 9, 7
Third-Line Options (When First Two Fail)
Baclofen and gabapentin are preferred third-line agents due to better long-term safety profiles compared to neuroleptics:
- Baclofen: Supported by randomized placebo-controlled trials; less likely to cause side effects during long-term therapy 7
- Gabapentin: Supported by small randomized trials with favorable safety profile 9, 7
Additional Breakthrough Options
- Haloperidol: 0.5-2 mg orally or IV every 4-6 hours 8
- Olanzapine: 5-10 mg orally daily (Category 1 evidence for breakthrough symptoms) 8
Etiology-Directed Treatment
If GERD is Suspected
- Initiate high-dose proton pump inhibitor therapy with response time variable from 2 weeks to several months 6
- Add prokinetic therapy (metoclopramide) if partial or no improvement occurs 6
- Implement antireflux diet and lifestyle modifications concurrently 6
If Pericardial Pathology is Suspected
- Obtain chest X-ray and echocardiography if hiccups suggest phrenic nerve compression from pericardial effusion 6
If Central Nervous System Cause is Suspected
- Consider corticosteroids (dexamethasone 4-8 mg BID-TID) for CNS involvement 8
- Brain tumors and traumatic brain injury are recognized central causes 6
Special Situations
Perioperative Hiccups
- For hiccups during anesthesia or post-extubation: Propofol 1-2 mg/kg IV may be effective 2
Refractory Cases
- Phrenic nerve blockade or surgical intervention (phrenic nerve crushing, blockade, or pacing) is reserved for medical refractory cases 3, 10
- Vagus nerve stimulator placement is emerging as a novel option with partial success reported in case series 3
Critical Monitoring Considerations
Complications of Untreated Persistent Hiccups
- Weight loss and depression can develop from untreated persistent hiccups 6
- Respiratory distress or laryngospasm can lead to post-obstructive pulmonary edema in severe cases 4
Safety Precautions with Chlorpromazine
- Reserve parenteral administration for bedfast patients or acute ambulatory cases 5
- Keep patient lying down for at least 30 minutes after injection due to hypotensive effects 5
- Elderly patients require lower doses and closer observation due to increased susceptibility to hypotension and neuromuscular reactions 1, 5