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Hiccups

Background
The term hiccup derives from the sound of the event; the alternative spelling
hiccough erroneously implies an association with respiratory reflexes. Brief episodes
of hiccups, which often induce annoyance in patients and merriment in observers,
are a common part of life. Prolonged attacks, however, are a more serious
phenomenon and often pose a diagnostic dilemma. These attacks have been
associated with significant morbidity and even death.
A hiccup bout is any episode lasting more than a few minutes. Hiccups lasting longer
than 48 hours are considered persistent or protracted. Hiccups lasting longer than 1
month are termed intractable. The longest recorded attack of hiccups lasted for 6
decades.

Pathophysiology
Hiccups appear to serve no purpose in humans or other mammals. Often, only a
single hemidiaphragm is affected. The left hemidiaphragm is affected in 80% of
cases, though bilateral involvement may occur.
Hiccups occur 4-60 times per minute until a certain number has been delivered.
Typically, this is fewer than 4 or more than 30. The frequency is relatively constant
for a given individual and varies inversely with arterial carbon dioxide tension
(PaCO2). The loudness and rapidity of hiccups are unrelated. Hiccups are more
common in the evening and may continue for a few waking hours. They occur most
frequently during the first half of the menstrual cycle, especially in the few days
before menstruation, and become markedly less frequent during pregnancy.
Despite centuries of contemplation, the exact pathogenesis of hiccups remains a
mystery. Hippocrates and Celsus associated hiccups with liver inflammation and
other conditions. Galen believed that hiccups were due to violent emotions arousing
the stomach. In 1833, Shortt first recognized an association between hiccups and
phrenic nerve irritation.
The hiccup reflex, originally proposed by Bailey in 1943, consists of the following:
Afferent limb - Phrenic and vagus nerves and sympathetic chain arising from T6-12
Hiccup center - Nonspecific location between C3 and C5
Connections to the respiratory center, phrenic nerve nuclei, medullary reticular
formation, and hypothalamus
Efferents - Phrenic nerve (C3-5), anterior scalene muscles (C5-7), external
intercostals (T1-11), glottis (recurrent laryngeal component of vagus),
inhibitory autonomic processes, decreasing esophageal contraction tone, and
lower esophageal sphincter tone

Etiology
The cause of hiccups in children and infants is rarely found. Brief episodes in adults
are usually benign and self-limiting. Typical causes include gastric distention (ie,
from food, alcohol, or air), sudden changes in ambient or gastric temperature, and
use of alcohol or tobacco in excess. Psychogenic causes (ie, excitement and stress)
also may elicit hiccups.

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Persistent or intractable episodes are more likely to result from serious
pathophysiologic processes affecting a component of the hiccup reflex mechanism.
More than 100 causes have been described; however, in many cases, the cause
remains idiopathic.
Eighty-two percent of persistent or intractable episodes occur in men. An organic
cause can be identified in 93% of men and in 8% of women, resulting in an overall
organic incidence of 80%; the remaining 20% of cases are considered psychogenic
in origin. Psychogenic conditions associated with hiccups include the following:
Hysteria
Shock
Fear
Personality disorders
Conversion disorders
Malingering
Central nervous system (CNS)-related causes of hiccups include the following:
Structural lesions - Congenital malformations, malignancies, or multiple sclerosis
Vascular lesions
Infection
Trauma
Conditions that can give rise to diaphragmatic irritation causing hiccups are as
follows:
Hiatal hernia
Subphrenic abscess or collection
MI
Pericarditis
Conditions associated with irritation of the following branches of the vagus nerve
irritation can cause hiccups:
Meningeal branches Meningitis or glaucoma
Auricular branches - Foreign body or hairs
Pharyngeal branches - Pharyngitis
Recurrent laryngeal nerve - Mass lesions in the neck, goiter, or laryngitis
Thoracic branches - Infection, tumors esophagitis (ie, reflux), myocardial infarction
(MI), asthma, trauma, thoracic aortic aneurysm, or pacemaker lead
complications
Abdominal branches - Tumors, gastric distention, peptic ulcer, abdominal aortic
aneurysm, infection, organ enlargement, or inflammation (eg, appendicitis,
cholecystitis, pancreatitis, or inflammatory bowel disease)
Procedure- or anesthesia-related causes of hiccups include the following :
Hyperextension of the neck - Stretching the phrenic nerve roots
Manipulation of the diaphragm or stomach
Laparotomy
Thoracotomy
Craniotomy
Metabolic causes of hiccups include the following:
Hyponatremia
Hypokalemia
Hypocalcemia

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Hyperglycemia
Uremia
Hypocarbia
Fever
Drugs associated with hiccups include the following:
Benzodiazepines
Short-acting barbiturates
Dexamethasone
Alpha-methyldopa

Epidemiology
Hiccups can occur at any age. They may even be observed in utero; preterm infants
spend up to 2.5% of their time hiccupping. Although hiccups occur less frequently
with advancing age, intractable hiccups are more common in adult life. Females
develop hiccups more frequently during early adulthood than males of the same age
do.
The overall incidence of hiccups is the same in males as it is in females; however,
protracted and intractable hiccups occur more frequently in men (82% of cases).

Prognosis
In general, hiccups are self-limited, and the prognosis is excellent. The prognosis of
protracted hiccups is related to that of the underlying etiology.
Protracted hiccups often are associated with underlying organic disease and often
induce social and emotional distress. Therapy must address causative and
complicating factors of protracted hiccups. Complications of hiccups may include the
following:
Arrhythmias
Gastroesophageal reflux
In prolonged cases, weight loss and sleep disturbance

History
No medical training is required to diagnose hiccups. For brief episodes that self-
terminate or that respond to simple maneuvers, no investigation or follow-up care is
necessary. In contrast, persistent and intractable hiccups frequently are associated
with an underlying pathological process and may induce significant morbidity. The
focus of the history, examination, and investigation is on identifying these causes
and effects. A full systemic inquiry, surgical history, and comprehensive drug history
may identify one of the many possible causes.
Hiccups that abate with sleep and temporally relate to stressful circumstances
commonly are psychogenic in origin. Arrhythmia-induced syncope has been reported
as both the cause and the effect of hiccups. Gastroesophageal reflux also may either
cause or result from hiccups. Weight loss, insomnia, and emotional distress may
complicate prolonged episodes. Alcoholism and acute alcohol ingestion may
contribute to the development of hiccups.


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Medical Treatment
Most hiccups will stop on their own. Home remedies are generally sufficient to
resolve hiccupping.
For persistent hiccups (lasting more than three hours) treatment varies.
A physician may prescribe medications for severe, chronic hiccups. Chlorpromazine
(Thorazine) is usually the first-line medication prescribed for hiccups. Other
medications used to treat hiccups include haloperidol (Haldol) and metoclopramide
(Reglan).
Some muscle relaxants, sedatives, analgesics, and even stimulants have also been
reported to help alleviate hiccup symptoms.
Phrenic nerve surgery (the nerve that controls the diaphragm) is a treatment of last
resort. This treatment is rarely performed and used only in cases that do not respond
to other treatments.

Practice Essentials
Brief episodes of hiccups are a common part of life; however, prolonged attacks are
a more serious phenomenon and have been associated with significant morbidity and
even death.
Signs and symptoms
No medical training is required to recognize hiccups. However, persistent and
intractable hiccups frequently are associated with an underlying pathologic process,
and efforts must be made to identify causes and effects. The history should address
the following:
Surgical history
Comprehensive drug history
Indicators of psychogenic origin
Arrhythmia-induced syncope
Gastroesophageal reflux
Weight loss
Insomnia
Emotional distress
Alcoholism and acute alcohol ingestion
A complete and focused physical examination may yield evidence of the following:
Head Foreign body or aberrant hair adjacent to tympanic membrane; glaucoma
Mouth - Pharyngitis
Neck Inflammation; mass lesions; goiter; voice abnormalities; stiffness
Chest Tumors; pneumonia; asthma
Cardiovascular system Arrhythmias; myocardial infarction (MI); pericarditis;
unequal pulses
Abdomen Gastric atony; organomegaly; subphrenic abscess; cholecystitis;
appendicitis; abdominal aortic aneurysm (AAA); pancreatitis; peritonitis

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Rectum Mass lesions
Nervous system Focal lesions; disordered higher mental function; indications of
multiple sclerosis
See Presentation for more detail.
Diagnosis
Laboratory testing is directed toward suspected abnormalities as follows:
Electrolytes - Hyponatremia, hypokalemia, hypocalcemia, and hyperglycemia
Renal function tests - Uremia
Liver function tests - Hepatitis
Amylase and lipase levels - Pancreatitis
White blood cell (WBC) count
Urine, sputum, or cerebrospinal fluid (CSF) - Infection
Imaging modalities that may be helpful in the workup include the following:
Chest radiography
Fluoroscopy of diaphragmatic movement
Computed tomography (CT) of the head, thorax, and abdomen
Magnetic resonance imaging (MRI)
Other studies that may be helpful include the following:
Electrocardiography
Nerve conduction studies
Endoscopy or bronchoscopy
Esophageal acid perfusion test
See Workup for more detail.
Management
A definitive cure for hiccups has not yet been established. Treatment, if needed, may
be pharmacologic or nonpharmacologic.
Pharmacologic therapies include the following:
Chlorpromazine (drug of choice)
Haloperidol
Metoclopramide
Phenytoin
Valproic acid
Carbamazepine
Gabapentin
Ketamine
Baclofen
Lidocaine
Other agents reported to be beneficial are as follows:
Muscle relaxants (not benzodiazepines, see Etiology)
Sedatives
Analgesics (eg, orphenadrine, amitriptyline, chloral hydrate, and morphine)
Stimulants (eg, ephedrine, methylphenidate, amphetamine, and nikethamide)
Miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, and
nifedipine)
Nonpharmacologic therapies include the following:

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Techniques affecting components of the hiccup reflex - Stimulation of the
nasopharynx; C3-5 dermatome stimulation; direct pharyngeal stimulation;
direct uvular stimulation; removal of gastric contents
Techniques leading to vagal stimulation - Iced gastric lavage; Valsalva maneuver;
carotid sinus massage; digital rectal massage; digital ocular globe pressure
Techniques interfering with normal respiratory function - Breath holding;
hyperventilation; gasping; breathing into a paper bag; pulling the knees up to
the chest and leaning forward; continuous positive airway pressure;
rebreathing 5% carbon dioxide
Mental distraction
Behavioral conditioning
Hypnosis
Acupuncture
Phrenic nerve or diaphragmatic pacing
Prayer
Surgical intervention (typically a last resort) may include the following:
Phrenic nerve ablation (unilateral or bilateral as appropriate)
Microvascular decompression of the vagus nerve (according to case reports)
See Treatment and Medication for more detail.

Differential Diagnoses
Acute Renal Failure
Anxiety
Appendicitis, Acute
Asthma
Brain Abscess
Bronchitis
Cholecystitis and Biliary Colic
Diaphragmatic Injuries
Encephalitis
Epidural and Subdural Infections
Esophagitis
Foreign Bodies, Ear
Gastroenteritis
Glaucoma, Acute Angle-Closure
Hepatitis
HIV Infection and AIDS
Hypocalcemia
Hypokalemia
Hyponatremia
Inflammatory Bowel Disease
Meningitis
Multiple Sclerosis
Myocardial Infarction
Myocarditis
Neoplasms, Brain
Neoplasms, Lung
Pancreatitis
Pericarditis and Cardiac Tamponade
Pneumonia, Aspiration
Pneumonia, Bacterial

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Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Pneumonia, Viral
Toxicity, Alcohols
Toxicity, Caustic Ingestions
Uremia

Laboratory Studies
A wide variety of conditions may contribute to hiccups. The possibilities are narrowed
down by the findings from the history and physical examination. Laboratory testing is
directed toward suspected abnormalities.
Electrolytes - Hyponatremia can be either the cause (including Addison disease) or
the effect (drinking water as a cure) of hiccups; other electrolyte-related
causes are hypokalemia, hypocalcemia, and hyperglycemia
Renal function tests - Uremia
Liver function tests - Hepatitis
Amylase and lipase levels - Pancreatitis
White blood cell (WBC) count
Certain infectious diseases may cause a patient to hiccup. Appropriate testing for
such infections may include the following:
Urine
Sputum
Cerebrospinal fluid (CSF)

Approach Considerations
Generations of physicians have failed to discover a definitive cure for hiccups. The
following statement from the Mayo Clinic, though made in 1932, still describes the
situation perfectly: "The amount of knowledge on any subject such as this can be
considered as being in inverse proportion to the number of different treatments
suggested and tried for it."
Patients rarely present to the emergency department (ED) after cessation of a brief
episode of hiccups. If this occurs, the possibility of another reason for the
presentation (eg, depression) should be considered first.
Supportive care is administered as indicated by the causative pathology (eg, oxygen
for the patient whose hiccups may be secondary to pneumonia). Therapy is directed
first toward at the cause of the hiccups (if identified) and then toward the hiccups
themselves (if necessary).
Gastroesophageal reflux is associated closely with hiccups but may be either a cause
or an effect. Acid perfusion studies should be done to confirm the inducibility of
hiccups before antireflux surgery is performed to cure hiccups.
Treatment may be pharmacologic or nonpharmacologic. Surgical phrenic nerve
ablation has been advocated for intractable cases that are unresponsive to other
treatment. This drastic approach may be associated with considerable morbidity and
is not universally successful. A Cochrane review concluded that the available
evidence was insufficient to guide treatment of persistent or intractable hiccups by
either pharmacologic or nonpharmacologic means

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Consultation is rarely necessary unless the cause of the hiccups calls for the
participation of a specialist.

Medication Summary

Pharmacologic Therapy
Various agents have been reported to cure hiccups. Of these, chlorpromazine is the
most thoroughly studied and appears to be the drug of choice. Regimens in the
range of 25-50 mg intravenously (IV) or intramuscularly (IM) are effective in 80% of
cases. To prevent or minimize hypotension caused by this agent, preloading the
patient with 500-1000 mL of IV fluid is advised.
Another major tranquilizer, haloperidol, is effective in doses of 2-5 mg.
Metoclopramide has been used successfully in a dosage of 10 mg every 8 hours.
Several anticonvulsant agents have been used to treat intractable hiccups.
Phenytoin, valproic acid, and carbamazepine have all been effective when used in
typical anticonvulsant doses. Gabapentin has been shown to be effective in patients
with central nervous system (CNS) lesions and in some other etiologic groups.
Of the anesthetic agents, ketamine has been the most successful in a dose of 0.4
mg/kg (one fifth of the usual anesthetic dose). The centrally acting muscle relaxant
baclofen, , in a dosage of 10 mg orally every 6 hours, is particularly useful in patients
for whom other agents are contraindicated (eg, those with renal impairment). IV
lidocaine, in a loading dose of 1 mg/kg followed by an infusion of 2 mg/min, has
cured patients after other agents were unsuccessful. Oral lidocaine was reported to
be successful in 4 cancer patients with hiccups.
Other agents reported to be beneficial are as follows:
Muscle relaxants
Sedatives
Analgesics (eg, orphenadrine, amitriptyline, chloral hydrate, and morphine)
Stimulants (eg, ephedrine, methylphenidate, amphetamine, and nikethamide)
Miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, and
nifedipine)
Benzodiazepines exacerbate or precipitate hiccups and should be avoided.[10]

Home Remedies for Hiccups
There are numerous home cures for hiccups. You can try these methods at home to
get rid of hiccups:
Methods that cause the body to retain carbon dioxide, which is thought to relax the
diaphragm and stop the spasms which cause the hiccups:
Hold your breath
Techniques that stimulate the nasopharynx and the vagus nerve, which runs from
the brain to the stomach, and can decrease hiccupping:

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Drink a glass of water quickly
Have someone frighten you
Pull hard on your tongue
Bite on a lemon
Gargle with water
Drink from the far side of a glass
Use smelling salts
Place one-half teaspoon of dry sugar on the back of your tongue. (This process
can be repeated three times at two-minute intervals. Use corn syrup, not
sugar, for young children.)