Diagnostics: Intractable Hiccups

Overview

Hiccups are one of the most common human reflexes and fascinatingly occur in adults, children, neonates and in utero! The official medical term for hiccups is “singultus” which is derived from the Latin root word singult and means “to catch one’s breath while sobbing”.  While there is no established purpose for hiccups in adults, it is hypothesized that its role in utero is to prevent amniotic fluid aspiration and for respiratory muscle and diaphragmatic training prior to delivery.  

In most cases, hiccups are a benign, self-limited, albeit annoying phenomenon. However, as hiccups become increasingly frequent or persistent, they can be distressing for patients and can be a sign of underlying disease. Prolonged hiccups can also cause a myriad of negative health consequences including sleep deprivation, exhaustion, malnutrition, dehydration, and depression. The physiology, etiology, and evaluation/management strategy of intractable hiccups remains poorly understood. As emergency medicine physicians, it is our job to discern concerning symptoms from the benign and recognize the subtle differences between them to guide appropriate therapy and disposition. This approach can be applied to the chief complaint of hiccups as it represents a largely benign process that can harbor underlying disease when persistent or intractable. This blog post will attempt to serve as a resource to assist in the evaluation of persistent/intractable hiccups and cover the physiology, classification, associated disease processes, evaluation and management strategies of hiccups in the emergency department.  

Epidemiology:

• Upwards of 4,000 admissions per year for evaluation/management of hiccups

• Intractable hiccups are more common in men

  • Non-CNS mediated hiccups have a strong male predominance with odds ratio of 11.72

  • CNS mediated hiccups do not exhibit gender predominance

• Prevalence of recurrent hiccups in advanced cancer patients is around 5%

• 20% of Parkinson’s patients reported frequent hiccups

• Recurrent hiccups are present in 10% of those with GERD.

Classification:

Hiccups are classified by their duration:

• Acute: < 48 hours

• Persistent: 48 hours - 1 month

• Intractable: > 1 month

Physiology:

First, let’s start with the basics. What is a hiccup? A hiccup is an involuntary sudden myoclonic contraction of the diaphragm and intercostal muscles with associated glottic closure. The abrupt halt in inspiration coupled with the closed glottis contributes to the “hic” sound.

 The action itself is thought to be carried out through a dopamine/GABA mediated reflex arc in which phrenic, vagal and sympathetic afferents carry impulses to the cervical spinal cord and dorsal medulla.  The efferent limb of the reflex is then carried out via the phrenic nerve.

Causes/Differential Diagnosis:

The leading theory behind benign, self-limited hiccups is that rapid stomach distention occurs following a large meal or carbonated beverage can alter the afferent limb of the reflex arc and trigger a hiccup. Smoking and experiencing intense emotions can also trigger episodes of acute hiccups.

For persistent and intractable hiccups, essentially any insult to this reflex arc, be it chemical, ischemic, inflammatory, infectious, neoplastic or drug induced can trigger hiccups. Consequently, the differential diagnoses for persistent and intractable hiccups are quite broad and includes the following:

• Gastrointestinal (Most Common Overall Etiology)

  The most common causes of persistent/intractable hiccups are GERD, peptic ulcer disease, and H.Pylori infections. Increased acid production can lead to disruption of the esophageal vagal afferent nerve fibers and trigger hiccups. In intubated and postoperative patients, gastric/peritoneal insufflation and distention is a common trigger for hiccups. Other causes include gastritis, gastric malignancy, pancreatitis, hiatal hernia, SBO, large meal, spicy foods, and carbonated drinks

• Neurologic

  Stroke, space occupying lesion, epilepsy, CNS infection, demyelinating and neurodegenerative disorders such as multiple sclerosis and Parkinson’s disease are causes of intractable hiccups. The most common lesion in those with intractable hiccups attributed to stroke is the lateral medulla. The medulla regulates cardiopulmonary function, reflexes, motor/sensory propagation and is the origin of cranial nerves IX, X, XI, and XII.  The posterior inferior cerebellar artery (PICA) supplies blood to the lateral medulla. A lateral medullary infarct can manifest as decreased pain and temperature sensation to the contralateral trunk and ipsilateral face, vertigo, nystagmus, diminished gag reflex, dysphagia, hoarseness, ataxia, ipsilateral Horner syndrome, and hiccups. The deficits associated with a lateral medullary infarct are classically referred to as Wallenberg syndrome. Cortical, subcortical and posterior strokes have also been rarely identified in those with intractable hiccups. Vascular lesions are the most common cause of CNS mediated intractable hiccups.  

• Neoplastic

  Malignancies can manifest as intractable hiccups by physically abutting or disrupting the reflex arc in the neck, esophagus, thorax, abdomen or CNS.

• Cardiopulmonary

  Myocardial ischemia has been identified in patients presenting with intractable hiccups with the proposed mechanism involving phrenic nerve irritation and reflex arc stimulation.  Additionally, cardiac instrumentation, recent procedures such as bronchoscopy/endoscopy, central venous catheter placement/displacement, aortic aneurysm, pneumonia, asthma, COPD, pleural effusion, and pericarditis can manifest as intractable hiccups through similar mechanisms.

• Pharmacologic

  Multiple medications have been associated with the development of hiccups. They include:

  • Dexamethasone

  • Azithromycin

  • Aripiprazole, Ropinirole, Pramipexole or other dopamine agonists

  • Ethanol

  • Opioids

  • Benzodiazepines

  • Chemotherapy agents such as cisplatin, folfirinox, carboplatin, irinotecan

• Psychogenic

  Anxiety, fear, stress, tic disorder have been associated with development of hiccups

• Other

  Electrolyte derangements (hyponatremia, hypokalemia, hypocalcemia), inhaled irritants

Key takeaway: Persistent or intractable hiccups without explanation warrant additional workup.

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Clinical Decision-Making Assistance

CC: Hiccups

Pertinent Historical Features:

Onset, duration, context, associated symptoms, relationship with sleep (persistence during sleep suggests complicated cause), provocative, palliative factors, current medications

Classification:

• Acute:  48 hrs

• Persistent: 48hrs-1 month

• Intractable: 1 month

Physical Exam:

Special consideration given to neurologic, cardiopulmonary, HEENT, and abdominal exams. Below are specific findings to evaluate for that may indicate a more serious cause of hiccups.

General appearance: Cachexia, jaundice, pallor

Neurologic exam: Cranial nerve/cerebellar deficit, strength/sensory deficit, reflex abnormality, dysphagia, gait disturbance

HEENT:  Foreign body in ear canal, head/neck mass, voice changes, lymphadenopathy

Cardiopulmonary: Murmur, friction rub, decreased breath sounds (pleural effusion/empyema), crackles, wheezes, rales, rhonchi, JVD, Pancoast syndrome

Gastrointestinal: Distension, hernia, ascites, tenderness, palpable mass, melena, hematochezia

Diagnostics: Diagnostic workup should be guided by historical features and physical examination

Laboratory Workup:

• CBC to evaluate for underlying infection, anemia

• CMP, lipase for electrolyte derangements/pancreatic/hepatobiliary dysfunction

• EKG, troponins, BNP if concerned for cardiac involvement

• ETOH, toxicologic workup if concerned for ingestion/intoxication

Imaging:

• CXR to evaluate for cardiopulmonary pathology (infiltrate, pleural effusion, mediastinal/pulmonary masses, etc.)

• CT head/CTA head/neck/MRI with neurology consultation if neurologic deficits are present on exam or other clinical concern for stroke/seizures/mass

• Consider CT abdomen/pelvis or CT chest if indicated to evaluate for malignancy

Treatment

Non-Pharmacologic

• Time

• Breath holding

• Vagal maneuvers

  • Valsalva, gag, cough, expiration through syringe

• Large glass of water

• Sour foods

• Drinking upside down

• Fear response

Pharmacologic

• Empiric Therapy: Proton Pump Inhibitors for treatment of presumed GERD

• First Line for Refractory Hiccups:

  • Metoclopramide 10 mg PO or IV

  • Gabapentin 300 mg PO TID

  • Baclofen 5 mg PO TID

• Second Line:

  • Chlorpromazine 25mg PO or IV

    • Note: PO preferred over IV administration due to risk of hypotension. If using IV route, patient should be supine for 30 minutes after administration and IV piggyback administration preferred

• Alternatives:

  • Haloperidol 5-10 mg PO or 2-5mg IM

  • Droperidol 1.25-2.5 mg IV

  • Olanzapine 2.5 mg PO

Disposition

• Acute isolated hiccups or persistent/intractable hiccups without identifiable or suspected secondary cause and/or sleep disturbance/exhaustion → generally appropriate discharge if able to tolerate PO

  • May prescribe PPI with GI referral for potential upper endoscopy, esophageal manometry, 24 hr pH reflux study, cross sectional imaging to evaluate for GERD or other GI etiology

• If workup has yielded identifiable or suspected secondary cause, or the patient is experiencing sleep deprivation/exhaustion secondary to hiccups → consult appropriate service as indicated for possible admission and further workup

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Authorship

Post by Charles Reed, MD

Dr. Reed is a PGY-1 in Emergency Medicine at the University of Cincinnati.

Editing by Arthur Broadstock, MD

Dr. Broadstock is an Assistant Professor of Emergency Medicine at the University of Cincinnati and an Assistant Editor of TamingtheSRU. He is a graduate from the UC EM residency, class of 2023.

Cite As: Reed, C. Broadstock, A. Diagnostics: Intractable Hiccups. TamingtheSRU. www.tamingthesru.com/blog/diagnostics/intractable-hiccups. 11/19/2024

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