What is the treatment for intractable hiccups?

Treatment of Intractable Hiccups

Chlorpromazine is the first-line pharmacological treatment for intractable hiccups, administered at 25-50 mg three to four times daily orally, or 25-50 mg intramuscularly or intravenously for severe cases. 1, 2

Definition and Classification

• Hiccups are sudden contractions of the diaphragmatic and intercostal muscles followed by laryngeal closure, producing the characteristic "hic" sound 3
• Classified as:
  • Acute: self-limited episodes
  • Persistent: lasting more than 48 hours
  • Intractable: lasting more than 2 months 3

First-Line Pharmacological Treatment

Chlorpromazine

• The only FDA-approved medication specifically for intractable hiccups 4
• Dosing:
  • Oral: 25-50 mg three to four times daily 1
  • Intramuscular: 25-50 mg every 3-4 hours as needed 2
  • Intravenous (for severe cases): 25-50 mg diluted in 500-1000 mL saline as slow infusion with patient lying flat 2
• Monitor blood pressure closely during parenteral administration due to risk of hypotension 2
• Inject IM doses slowly into the upper outer quadrant of buttock and keep patient lying down for at least 30 minutes after injection 2

Alternative Pharmacological Options

If chlorpromazine is ineffective or contraindicated, consider:

• Baclofen: One of the few agents studied in randomized controlled trials 4
• Gabapentin: Studied in prospective trials with positive results 4
• Metoclopramide: Studied in randomized controlled trials; also addresses gastroparesis if present 5, 4
• Haloperidol: Alternative neuroleptic option 4
• Amitriptyline, midazolam, nifedipine, nimodipine, orphenadrine, or valproic acid: Case reports support efficacy 4

Combination Therapy Approach

For refractory cases, consider a stepwise approach:

1. Start with a dopamine receptor antagonist (chlorpromazine, haloperidol, metoclopramide, or olanzapine) titrated to maximum benefit and tolerance 5
2. If hiccups persist, add a 5-HT3 antagonist (e.g., ondansetron) with or without an anticholinergic agent (e.g., scopolamine) and/or antihistamine (e.g., meclizine) 5
3. If still ineffective, add a corticosteroid (e.g., dexamethasone) with or without olanzapine (if not already tried) 5
4. For intractable cases, consider continuous IV/subcutaneous infusion of antiemetics 5

Non-Pharmacological Interventions

For cases refractory to medication:

• Nerve blockade: Phrenic nerve or vagal nerve blocks may provide relief 6
• Nerve stimulation: Vagus nerve stimulation has shown promise in case reports 6
• Surgical options:
  • Microvascular decompression of the vagus nerve when neurovascular compression is suspected 7
  • Phrenic nerve crushing or resection as a last resort 6
• Alternative approaches: Acupuncture, hypnosis, and breathing techniques 3, 6

Special Considerations

Underlying Causes

Always investigate and treat potential underlying causes:

• Central causes: Stroke, space-occupying lesions, brain injury 3
• Peripheral causes: Tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease 3
• Medication-induced: Anti-parkinsonism drugs, anesthetics, steroids, chemotherapy 3
• Metabolic: Electrolyte abnormalities, uremia 3

Cautions

• Monitor for QT prolongation with chlorpromazine and other antipsychotics 5
• Use lower doses in elderly, debilitated, or emaciated patients 1, 2
• Be cautious with chlorpromazine in patients taking other medications with anticholinergic properties 5
• For patients with high respiratory rates, deliver oxygen via Venturi mask at flow rates exceeding their peak inspiratory flow if respiratory support is needed 5

Treatment Algorithm

1. Confirm diagnosis of intractable hiccups (lasting >2 months)
2. Investigate and treat underlying causes
3. Start chlorpromazine 25-50 mg TID-QID orally
4. If severe or oral route not feasible, use IM/IV chlorpromazine
5. If ineffective after 2-3 days, consider alternative agents (baclofen, gabapentin, metoclopramide)
6. For refractory cases, implement combination therapy as outlined above
7. Consider non-pharmacological interventions if medications fail