Cite as: Shah PC, Jindal A. Management of intractable hiccups: modern insights for pain physicians. ASRA Pain Medicine News 2026;51. https://doi.org/10.52211/asra080126.011.

Introduction

Hiccups are involuntary spasmodic contractions of the diaphragm and intercostal muscles followed by abrupt glottic closure. Although usually benign and short-lived, hiccups may persist beyond 48 hours (“persistent”) or for more than one month (“intractable”), leading to impaired sleep, nutritional compromise, depression, and significantly reduced quality of life.¹

Due to the disease’s complex pathophysiology, which involves the peripheral and central nervous systems and the musculature, no single specialty is responsible for its management. Gastroenterology, neurology, neurosurgery, oncology, otolaryngology, and even other specialties may each contribute to initial evaluation and first-line pharmacologic management, but once these measures fail, no specialty owns the next step.² Pain physicians — whether in chronic pain, acute pain, or regional anesthesiology — are uniquely positioned to fill this void by using real-time imaging to access the precise neural structures driving the reflex procedures. These procedures fall within the pain physician’s skill set but are outside the scope of any other specialty, with service-specific consultation based on institutional practice.

Reflex Arc and Pathophysiology

The hiccup reflex arc comprises afferent pathways (vagus nerve, phrenic nerve, and thoracic sympathetic fibers), central processing (medullary structures near the respiratory centers), and efferent outputs (phrenic nerve to the diaphragm, spinal nerves to the intercostal muscles, and the recurrent laryngeal nerve causing glottic closure).³ Neurotransmitters implicated in hiccups include dopamine, gamma-aminobutyric acid (GABA), and serotonin, informing the diverse pharmacologic targets utilized clinically. Intractable hiccups often arise from multifactorial triggers, including gastroesophageal reflux disease (GERD), central nervous system pathology, thoracic or abdominal irritation, metabolic derangements (eg, hyponatremia), medication effects, and malignancy.⁴ A thorough history and physical examination are crucial and should include targeted laboratory studies and imaging as indicated.

Corticosteroids deserve special mention as one of the most well-established pharmacologic triggers, making intractable hiccups directly relevant to pain physicians who routinely co-administer dexamethasone for epidural injections, nerve blocks, and joint procedures. Proposed mechanisms include competitive binding to corticosteroid receptors within the afferent limb of the hiccup reflex arc and lowering of synaptic transmission thresholds in the midbrain,⁵ with high-dose dexamethasone (10 mg) appearing more strongly implicated than other steroids. In a prospective study, the incidence was found to be as high as 42% in patients receiving dexamethasone.⁵ Malignancy is another important trigger, where mediastinal or abdominal tumors, hepatomegaly, ascites, or gastric distension can cause phrenic nerve or diaphragmatic irritation; hiccups in this population are also associated with chemotherapy and corticosteroid use.⁶

Updated Pharmacologic Strategies

Although chlorpromazine remains the only U.S. Food and Drug Administration (FDA)-approved agent specifically indicated for hiccups, most pharmacologic evidence derives from case series and expert consensus.⁶ Baclofen, a GABA-B agonist, and gabapentin, a calcium channel modulator and GABA analog, are frequently used due to favorable safety profiles, with baclofen demonstrating reduced hiccup severity in controlled trials and reviews.^4,6 Metoclopramide, a dopamine antagonist and prokinetic, provides added benefit in cases associated with GERD.⁶

Emerging pharmacologic evidence includes amitriptyline for refractory idiopathic hiccups, which has been reported to improve symptoms when added to other therapies, suggesting a role for tricyclics in select patients.⁷ In oncology cohorts, steroid rotation (eg, replacing dexamethasone or omitting it altogether), the use of baclofen, and even the use of olanzapine have shown benefit in reducing hiccup frequency and severity.¹

Perioperative and Acute Management

Perioperative hiccups can impede ventilation and surgical exposure and may be triggered by airway manipulation, gastric insufflation, or anesthetic agents. A narrative review emphasizes the importance of identifying perioperative triggers and applying targeted treatment, including modulation of anesthetic depth and supportive measures in addition to pharmacotherapy.³

Interventional and Regional Approaches

When conservative therapy fails, a range of targeted interventions are available. Ultrasound-guided phrenic nerve block directly interrupts the efferent limb of the hiccup reflex by anesthetizing diaphragmatic motor fibers. Contemporary case literature demonstrates successful termination of persistent hiccups with combined ultrasound and nerve stimulator-guided phrenic nerve blockade, leading to immediate cessation and short-term symptom resolution without adverse effects.⁸ However, recent case series caution that results are inconsistent, with variable durations of relief and occasional adverse effects, highlighting the need for careful patient selection.⁹ Adverse events are mostly derived from ipsilateral diaphragmatic paresis, leading to a 20%-30% reduction in pulmonary function.^10,11 Patients unable to tolerate this reduction—including those with moderate-to-severe obstructive lung disease, obstructive sleep apnea, morbid obesity, and pre-existing contralateral phrenic nerve palsy—are poor candidates. Ultrasound evaluation of bilateral diaphragmatic movement prior to the procedure is recommended to identify pre-existing asymmetry and guide side selection.

When phrenic nerve blocks provide only temporary relief, pulsed radiofrequency modulation of the phrenic nerve offers a longer-duration alternative by modulating nerve function without causing destructive lesioning.^12,13

Intractable hiccups present a significant clinical challenge with diverse etiologies and limited standardized treatment protocols. 

Stellate ganglion block targets the sympathetic component of the hiccup reflex arc. Case reports suggest it may provide temporary symptom relief in refractory hiccups when vagal maneuvers and pharmacologic therapy fail.¹⁴ Stellate ganglion block has been used both as a standalone intervention and in combination with phrenic nerve block, with the combined approach showing synergistic benefit in postoperative and chronic intractable hiccups.¹⁵ While mechanistically appealing given sympathetic afferent contributions to the hiccup reflex, evidence remains limited to small case series.

There may also be a role for continuous cervical epidural block at C3-C5, which has shown complete remission of intractable hiccups in a case series of 28 patients.¹⁶

A novel intervention involves ultrasound-guided placement of phrenic nerve peripheral nerve stimulation (PNS) leads. In a peer-reviewed case report in Regional Anesthesia & Pain Medicine, bilateral phrenic nerve PNS resulted in substantial improvement in chronic intractable hiccups after traditional therapies failed, improving the patient’s quality of life without complications.¹⁷ This technique underscores the potential role of neuromodulation where standard interventions are inadequate, though prospective data are lacking.

Vagal nerve stimulation (VNS) has been reported with mixed results. One case of post-stroke intractable hiccups achieved complete resolution with VNS implantation;¹⁸ however, another patient with idiopathic intractable hiccups had no benefit despite 8 months of VNS with multiple parameter adjustments.¹⁹

Emerging reports describe phrenic nerve cryoablation as a novel approach to interrupt the motor limb of persistent hiccups, though data remain limited to preliminary cases.²⁰ Such techniques are investigational but represent future possibilities for refractory disease.

Non-Pharmacologic and Supportive Approaches

Non-interventional strategies, such as vagal maneuvers and controlled breathing, are widely used acutely, and more evidence is being collected for intractable cases. Acupuncture^21,22 and osteopathic manipulative techniques (OMT)²³ have been reported as adjunctive options in select clinical contexts.

Proposed Clinical Algorithm

1. Identify and treat reversible triggers (GERD, metabolic abnormalities, offending medications).
2. Initiate pharmacologic therapy (chlorpromazine, baclofen, gabapentin; escalate combination therapy as needed).
3. Evaluate for interventional solutions (phrenic nerve block, PNS) in refractory or debilitating cases.
4. Consider advanced neuromodulation or procedural strategies (stellate ganglion block, pulsed radiofrequency, cryoablation) on a case-by-case basis.
5. Clinical judgment remains central to management, including supportive approaches (acupuncture, OMT). Collaborative care involving gastroenterology, neurology, palliative care, and interdisciplinary pain teams may optimize outcomes, particularly in complex cases.

Conclusion

Intractable hiccups present a significant clinical challenge with diverse etiologies and limited standardized treatment protocols. Chronic pain, acute pain, and regional anesthesiology physicians possess the procedural expertise and anatomic knowledge to intervene at multiple points along the hiccup reflex arc. Current evidence supports the judicious use of pharmacologic agents, targeted nerve blocks, and emerging neuromodulatory strategies. As research continues to evolve, physicians must integrate available data with individualized clinical assessment to achieve the best patient outcomes.

References

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