What is the definition and management of intractable hiccups?

Management of Intractable Hiccups

Definition

Intractable hiccups are defined as hiccups persisting for more than 2 months, distinguishing them from persistent hiccups (lasting 48 hours to 2 months) and acute hiccups (lasting less than 48 hours). 1, 2

• The mechanism involves a complex reflex arc with a supraspinal hiccup center, multiple neurotransmitters, and anatomical structures within the central and peripheral nervous system 2, 3
• Bilateral synchronous firing of the hemidiaphragm, anterior scalene, and intercostal muscles occurs, supporting the concept of a central hiccup center rather than isolated phrenic nerve involvement 3

First-Line Pharmacological Treatment

Initiate treatment with chlorpromazine, the FDA-approved medication for intractable hiccups, starting at 25-50 mg orally three to four times daily. 4, 5, 6, 7

• If oral therapy fails after 2-3 days, switch to intramuscular administration at 25-50 mg IM 5, 7, 8
• Chlorpromazine acts as a dopamine receptor antagonist, likely interrupting the hiccup reflex arc at the medullary level 5
• Critical monitoring: Check QTc interval before and during treatment, as chlorpromazine prolongs QT interval, especially with concurrent QT-prolonging medications 5, 6
• Watch for dystonic reactions, orthostatic hypotension, and extrapyramidal symptoms; have diphenhydramine 25-50 mg available for acute dystonia 5
• Use lower doses in elderly, debilitated, or emaciated patients who are more susceptible to hypotension and neuromuscular reactions 7

Second-Line Alternatives

If chlorpromazine is ineffective or not tolerated, consider these dopamine antagonists:

• Metoclopramide 10-20 mg orally or IV every 4-6 hours, particularly useful when gastroparesis or gastric outlet obstruction contributes to hiccups, as it provides dual benefit as both a prokinetic and dopamine antagonist 5
• Haloperidol 0.5-2 mg orally or IV every 4-6 hours, commonly used in palliative care settings, though carries risk of extrapyramidal symptoms and QTc prolongation 5
• Olanzapine, titrated to maximum benefit and tolerance 4, 6
• Monitor all dopamine antagonists for dystonic reactions and have diphenhydramine available 5

Escalation Strategy for Refractory Cases

If hiccups persist despite dopamine antagonist therapy, add combination therapy in a stepwise manner:

Step 1: Add Serotonergic and Anticholinergic Agents

• Add a 5-HT3 antagonist (ondansetron) with or without an anticholinergic agent (scopolamine) and/or antihistamine (meclizine) 4, 6

Step 2: Add Corticosteroid

• Add dexamethasone with or without olanzapine (if not already tried as the initial dopamine antagonist) for cases where underlying inflammation or malignancy may be contributing 4, 6

Step 3: Non-Pharmacological Interventions

• Consider nerve blockade or nerve stimulation if medications fail 4
• Nebulized lidocaine may be considered as a last resort for truly refractory cases, though assess aspiration risk first 5

Critical Diagnostic Considerations

Before initiating treatment, assess for underlying causes requiring specific treatment, as intractable hiccups often indicate serious pathology:

• Posterior inferior cerebellar infarction: Requires urgent neuroimaging, particularly in patients with altered consciousness, ataxia, or cranial nerve findings 6
• Metabolic abnormalities: Identify and correct electrolyte disturbances before initiating pharmacological treatment 5
• GERD, CNS lesions, gastric distension, and malignancy 5
• Area postrema syndrome: Intractable hiccups with nausea and vomiting may indicate MOG encephalomyelitis 5
• Medications, cardiac, pulmonary, and gastrointestinal etiologies 1

Alternative Agents for Special Circumstances

• Baclofen and gabapentin have been reported successful in some cases, though evidence is primarily anecdotal 2
• Tetrabenazine may be valuable for poststroke hiccups in patients intolerant or unresponsive to classic antipsychotic agents 9

Common Pitfalls

• Failing to investigate serious underlying causes while treating symptomatically—intractable hiccups are rarely idiopathic and often signal significant pathology 1, 2
• Inadequate monitoring for QTc prolongation with antipsychotic agents, especially in elderly patients or those on multiple medications 5, 6
• Premature escalation without allowing adequate trial of first-line therapy (2-3 days oral, then parenteral if needed) 7, 8
• Not having diphenhydramine immediately available when using dopamine antagonists 5