Hiccough / Hiccup (also spelled hiccough) is an involuntary contraction (myoclonic jerk) of the diaphragm that may repeat several times per minute. The hiccup is an involuntary action involving a reflex arc.[rx] Once triggered, the reflex causes a strong contraction of the diaphragm followed about 0.25 second later by closure of the vocal cords, which results in the classic “hic” sound.
Hiccups are diaphragmatic muscle contractions with early glottis closure terminating inspiration. They are involuntary and spasmodic, and often involve inspiratory intercostal muscle contractions. Hiccups are a common experience and warrant treatment only when they become persistent and bothersome. If persistent, they can affect conversation, concentration, and oral intake, and can lead to frustration, fatigue, and insomnia. They might contribute to an increase in pain.
Pathophysiology of Hiccough
The pathophysiological mechanism of hiccup is related to lesions in its reflex arc shown in Figure. The hiccup reflex arc consists of 3 components, the afferent limb including phrenic, vagus and sympathetic nerves to convey somatic and visceral sensory signals, the central processing unit in the midbrain and the efferent limb traveling in motor fibers of phrenic nerves to the diaphragm and accessory nerves to the intercostal muscles, respectively.[rx,rx,rx] Central process of hiccup remains poorly understood, it may not only be confined to the medulla but may also involve other parts of the central nervous system (CNS) located between the brainstem and cervical spine.[rx] The hiccup central component usually refers to chemoreceptors probably located in the periaqueductal gray matter and sub-thalamic nuclei.[rx] Among the neurotransmitters involved in the process of a hiccup, both dopamine (D) and gamma-aminobutyric acid (GABA) have been documented.[rx] The above pathophysiological basis explains why some inhibitors of these substances may be employed in the treatment of hiccup. Accordingly, any physical and chemicals irritants and inflammatory and neoplastic conditions involving the hiccup reflex may cause a hiccup. In addition, hiccup may be transient in many patients as the spontaneous resolution of the stimuli that caused it might lead to its disappearance.[rx] Unfortunately, owing to the long trajectory of afferent and efferent nerves and the diffuse central processes involving the hiccup reflex arc, the accurate diagnosis of lesions in the arc and trying to terminate the pathological processes in the intractable events are often very difficult.[rx] As several types of a lesion located along the hiccup reflex arc may cause it, hiccup is common and has been described as case reports in association with several conditions and has been treated with various types of treatment, which might confuse readers.
A hypothesis seeking to explain the purpose of the hiccup should meet the following criteria in order to be considered plausible:
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The hypothetical stimulus of the hiccup should be anatomically consistent with the afferent limb of the reflex.
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The activation of the efferent limb of the reflex should resolve or help to resolve the condition that leads to the stimulus. Ideally, the condition should explain all of the components of the efferent limb.
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The hypothesis should offer an explanation for the hiccup’s prevalence in mammals and its profoundly increased incidence during infancy.
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The resolution of the condition that is hypothesized to stimulate the hiccup should offer a tangible evolutionary advantage.
Causes of Hiccough
Pathophysiological causes
- Swallowing air excessively[rx]
- Gastroesophageal reflux[rx]
- Hiatal hernia[rx]
- Rapid eating[rx]
- Carbonated beverages, alcohol, dry breads, and some spicy foods[rx]
- Opiate drug use[rx]
- Laughing[rx]
Hiccups may be triggered by a number of common human conditions. In rare cases, they can be a sign of serious medical problems.
Pre-phrenic nucleus irritation of medulla
- Kidney failure[rx]
CNS disorders
Nerve damage
- Damage to the vagus nerve after surgery[rx]
A cause of long-term hiccups is damage to or irritation of the vagus nerves or phrenic nerves, which serve the diaphragm muscle. Factors that may cause damage or irritation to these nerves include:
- A hair or something else in your ear touching your eardrum
- A tumor, cyst or goiter in your neck
- Gastroesophageal reflux
- Sore throat or laryngitis
Central nervous system disorders
A tumor or infection in your central nervous system or damage to your central nervous system as a result of trauma can disrupt your body’s normal control of the hiccup reflex. Examples include:
- Encephalitis
- Meningitis
- Multiple sclerosis
- Stroke
- Traumatic brain injury
- Tumors
Metabolic disorders and drugs
Long-term hiccups can be triggered by
- Alcoholism
- Anesthesia
- Barbiturates
- Diabetes
- Electrolyte imbalance
- Kidney disease
- Steroids
- Tranquilizers
Causes of persistent hiccups
| Central nervous system disorders | Vascular | |
| Ischaemic/hemorrhagic stroke, AV malformations, temporal arteritis Infections | ||
| Encephalitis, meningitis, brain abscess, neurosyphilis, subphrenic abscess Structural | ||
| Head trauma, intracranial neoplasms, brainstem neoplasms, multiple sclerosis, syringomyelia, hydrocephalus | ||
| Vagus and phrenic nerve irritation | Goitre, pharyngitis, laryngitis, hair or foreign-body irritation of tympanic membrane, neck cyst or another tumor | |
| Gastrointestinal disorders | Gastric distention, gastritis, peptic ulcer disease, pancreatitis, pancreatic cancer, gastric carcinoma, abdominal abscesses, gallbladder disease, inflammatory bowel disease, hepatitis, aerophagia, oesophageal distention, oesophagitis, bowel obstruction | |
| Thoracic disorders | Enlarged lymph nodes secondary to infection or neoplasm, pneumonia, empyema, bronchitis, asthma, pleuritis, aortic aneurysm, mediastinitis, mediastinal tumours, chest trauma, pulmonary embolism | |
| Cardiovascular disorders | Myocardial infarction, pericarditis | |
| Toxic–metabolic | Alcohol | Diabetes mellitus |
| Herpes zoster | Hypocalcaemia | |
| Hypocapnia | Hyponatraemia | |
| Influenza | Malaria | |
| Tuberculosis | Uraemia | |
| Postoperative | General anaesthesia | Gastric distention |
| Intubation (stimulation of glottis) | Traction on viscera | |
| Neck extension (stretching phrenic nerve roots) | ||
| Drugs | Alpha-methyldopa | Dexamethasone |
| Short-acting barbituates | Diazepam | |
| Chemotherapeutic agents (for example, carboplatin) | ||
| Psychogenic | Anorexia nervosa | Malingering |
| Conversion reaction | Schizophrenia | |
| Excitement | Stress | |
This article describes an unusual cause of persistent hiccups and considers some of the remedies that can be used for the condition.
What Causes Hiccough?
Many conditions are associated with hiccups, but none has been shown to be the cause of hiccups.
- If a person eats too fast, he or she can swallow air along with food and end up with the hiccups.
- Smoking or chewing gum also can cause a person to swallow air and get hiccups.
- Any other practices that might irritate the diaphragm such as eating too much (especially fatty foods) or drinking too much (alcohol or carbonated drinks) can make a person prone to having hiccups.
- In these instances, the stomach, which sits underneath and adjacent to the diaphragm, is distended or stretched. As they occur in relation to eating and drinking, hiccups are sometimes thought to be a reflex to protect a person from choking.
- Strokes or brain tumors involving the brain stem, and some chronic medical disorders (such as renal failure) are reported to cause hiccups; trauma to the brain, meningitis, and encephalitis also may cause hiccups.
- Damage to the vagus or phrenic nerve may cause hiccups to last a long time.
- Problems with the liver, including swelling, infection, or masses can cause irritation of the diaphragm, which can cause hiccups.
- Some medications that can cause acid reflux may also have hiccups as a side effect. Most benzodiazepines, including diazepam (Valium), alprazolam (Xanax) and lorazepam (Ativan) can cause hiccups. In addition, medications such as levodopa (Larodopa), nicotine, and ondansetron (Zofran) can cause hiccups. Other medications that can cause hiccups include levodopa, methyldopa (Aldomet), nicotine, ondansetron (Zofran), barbiturates, opioid pain relievers, corticosteroids, anesthesia, or chemotherapy medications.
- Noxious fumes can also trigger hiccup symptoms.
- A baby may hiccup after crying or coughing. This is common in babies in the first year. In some instances, babies with gastroesophageal reflux (GERD) could be more prone to hiccups.
- Anxiety and stress can induce both short and long-term hiccups
Symptoms of Hiccough
- treatment a single or a series of breathing diaphragm spasms, of variable spacing and duration
- A brief (less than a one-half second), unexpected, shoulder, abdomen, throat, or full body tremor
- Hiccups may present as an audible chirp, squeak, “hupp”, or if controlled, a quick inhaling gasp, sigh, or sniff.
- Hiccups may present as brief but distracting or painful, frequent or occasional interruptions in normal breathing, with sudden momentary pain of the throat, chest, and/or abdomen.
Diagnosis of Hiccough
During the physical exam, your doctor may perform a neurological exam to check your:
- Balance and coordination
- Muscle strength and tone
- Reflexes
- Sight and sense of touch
If your doctor suspects an underlying medical condition may be causing your hiccups, he or she may recommend one or more of the following tests.
Laboratory Tests
Samples of your blood may be checked for signs of
- Diabetes
- Infection
- Kidney disease
- Blood tests, to check for infection, kidney disease or diabetes
Imaging Tests
- Imaging tests, such as an x-ray, CT, or MRI scan, to assess for any anatomical abnormalities which may be affecting the phrenic or vagus nerves or the diaphragm
- Endoscopic test, in which an endoscope, a flexible tube with a small camera at the end, is passed down the patient’s throat to check the windpipe or esophagus
- An electrocardiogram (ECG), to check for heart-related conditions by measuring electrical activity in the heart
These types of tests may be able to detect anatomical abnormalities that may be affecting the vagus nerve, phrenic nerve or diaphragm. Imaging tests may include:
- Chest X-ray
- Computerized tomography (CT)
- Magnetic resonance imaging (MRI)
Endoscopic Tests
These procedures utilize a thin, flexible tube containing a tiny camera, which is passed down your throat to check for problems in your esophagus or windpipe.
Treatment of Hiccough
Antipsychotic medications
- Chlorpromazine – Chlorpromazine is the only medication approved for hiccups by the US Food and Drug Administration, and for many years it was the drug of choice.[rx] Chlorpromazine is a dimethylamine derivative of phenothiazine. It acts centrally by dopamine antagonism in the hypothalamus. It has serious potential side effects, such as hypotension, urinary retention, glaucoma, and delirium, so it is generally no longer recommended as first-line management. A usual dosage would be 25 mg 4 times a day, increasing to 50 mg 4 times a day if needed.
- Haloperidol – Haloperidol has been shown to be effective, presumably also via dopamine antagonism. It might be better tolerated than chlorpromazine is.
Anticonvulsants
- Valproic acid – enhances GABA transmission centrally, and is similarly thought to aid in blocking the hiccup stimulus. Older anticonvulsants (valproic acid, phenytoin, carbamazepine) have been documented as potential treatments of hiccups for a number of decades, but challenges around their use include drug interactions and narrow therapeutic windows.
- Gabapentin – a newer antiepileptic drug commonly used in cancer and palliative medicine for neuropathic pain management, produces a blockade of neural calcium channels and increases release of GABA, which might modulate diaphragmatic excitability.
- Gabapentin has no known serious drug interactions and is not hepatically metabolized. One study involving 43 patients noted improvement and reduction of hiccups in 32 patients with 900-mg doses daily and in 9 patients with 1200-mg doses daily.[rx] In all patients, gabapentin was given as an initial drug for the treatment of hiccups. There were no severe adverse effects observed. Twelve patients had transient sleepiness.
Defoaming Agents
- Defoaming agents such as simethicone might be helpful if gastric distention is present.
Prokinetic Agents
- Defoaming agents might work well with prokinetic agents such as domperidone and metoclopramide, which help empty the stomach of its contents. Metoclopramide also has central dopamine antagonism but less so than chlorpromazine.
Peppermint
- Peppermint facilitates belching by relaxing the lower esophageal sphincter. Although this has been noted as a potential treatment of hiccups, there is little sense in using it along with a prokinetic agent, as their effects are somewhat opposite.[rx]
Proton pump inhibitors
- Proton pump inhibitors are important in the treatment of gastroesophageal reflux, which promotes hiccups. Proton pump inhibitors are generally safe and might be helpful in some cases.
Baclofen
- Baclofen in dosages of 5 mg twice daily to 20 mg 3 times daily has been shown to be effective in alleviating hiccups in several small trials and case series since 1992.[rx,rx,rx,rx] Although there are no well designed, large clinical trials, this GABA analog leads to a perceptual blockage in synaptic transmission and is now considered the drug of choice for the treatment of hiccups.
- It does have limitations. It might not be well tolerated owing to potential ataxia, delirium, dizziness, and sedation. Baclofen-related delirium is more common in patients with renal failure; however, specific dose modifications for a reduced glomerular filtration rate have not been defined.
Nifedipine
- Nifedipine, 10 to 20 mg orally or sublingually, might play a role in reversing the abnormal depolarization in the hiccup reflex arc, and case reports have shown it to be effective.[rx] But there is a substantial risk of inducing hypotension, which might be especially severe in relatively volume-depleted patients, such as many of those receiving palliative care.
Methylphenidate
- The neurostimulator methylphenidate might decrease hiccups through inhibition of dopamine and norepinephrine uptake.[rx] It might be a good choice in patients with concurrent depression or opioid-induced sedation, for which it might also be helpful.
Midazolam
- Midazolam has been used effectively, administered as a continuous intravenous or subcutaneous infusion, short of producing sedation.[rx]
Lidocaine
- Intravenous infusion of lidocaine has terminated hiccups in postoperative patients, but there is considerable risk of cardiovascular and neurologic toxicities, particularly in patients with advanced disease.[rx] Nebulized lidocaine might be effective on sensory nerves, and it has a better side effect profile; however, risks of aspiration after nebulization should be considered.
Dexamethasone
- Dexamethasone, although a main cause of hiccups, has been shown to terminate hiccups in AIDS-related progressive multifocal leukoencephalopathy, perhaps via its effects on edema.
Sertraline
- Sertraline might be beneficial, acting via peripheral serotonin receptors in the gastrointestinal tract, reducing abnormal esophageal, gastric, or diaphragmatic mobility, or through more central effects on the hiccup reflex arc.
Medication Combinations
- Medication combinations have been reported as successful in ameliorating hiccups. Baclofen and gabapentin have each been shown to be useful in conjunction with omeprazole and cisapride, and the use of all 4 medications has also been helpful.[rx]
- However, cisapride is no longer available owing to its serious side effects. The benefit of using multiple medications must always be balanced against the potential side effects, particularly in a patient population with a large burden of illness who already frequently take a number of other medications.
Self-Care and Folk Remedies
- There are many superstitious and folk remedies for hiccups, including headstand, drinking a glass of water upside-down, being frightened by someone, breathing into a bag, and eating a large spoonful of peanut butter. Placing sugar on or under the tongue has also been used.[rx][rx]
- Simple treatment involves increasing the partial pressure of CO2 and inhibiting diaphragm activity by holding one’s breath or rebreathing into a paper bag.[rx] Other potential remedies suggested by NHS Choices include pulling your knees up to your chest and leaning forward, sipping ice-cold water and swallowing some granulated sugar.[rx]
- Persistent digital rectal massage – has also been proven effective in terminating intractable hiccups.[rx] It is notable, that an Ig Nobel Prize has been awarded for this discovery. Later in an interview the laureate, Francis Fesmire explained another, probably more popular, treatment for hiccups: An orgasm results in incredible stimulation of the vagus nerve. From now on, I will be recommending sex – culminating with orgasm – as the cure-all for intractable hiccups.”[rx]
Non-pharmacological Measures to Treat Hiccups
- Phrenic nerve blockades such as ultrasound-guided blocking of efferent limbs, trans-esophageal diaphragmatic pacing, and nerve stimulator to confirm the effective blocking were successfully used to treat persistent post-operative and lung cancer-related hiccups.[rx,rx] Even a left vagal afferent blockade via nerve stimulation might be applied to stroke-related intractable hiccup after the failure of phrenic nerve block.[rx] Ultrasound-guided pulsed radiofrequency ablation of phrenic nerve was another option to treat coronary by-pass surgery related hiccup.[rx] Acupuncture has been employed to treat serious hiccups among patients with myocardial infarction and metastatic liver tumor.[rx,rx] A controlled trial confirmed that this procedure was superior over Ritalin to treat stroke-related hiccups.[rx]
References
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