Hiccups: The Right Clinical Information, Right Where It's Needed

Hiccups
The right clinical information, right where it's needed
Last updated: Aug 24, 2018

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 5
Prevention 6
Primary prevention 6
Secondary prevention 6
Diagnosis 7
Case history 7
Step-by-step diagnostic approach 7
Risk factors 9
History & examination factors 10
Diagnostic tests 11
Differential diagnosis 14
Diagnostic criteria 14
Treatment 15
Step-by-step treatment approach 15
Treatment details overview 16
Treatment options 18
Follow up 22
Recommendations 22
Complications 22
Prognosis 23
References 25
Disclaimer 27
Summary
◊ Hiccups is a common and mostly harmless condition.
◊ Most hiccups are benign and self-limiting, rarely requiring medical attention. However, various
organic and psychogenic causes can lead to persistent, intractable hiccups that can last for years.
◊ Persistent intractable hiccups can lead to malnutrition, weight loss, dehydration, fatigue, depression,
insomnia, and reduced quality of life.
◊ Various therapies have been described, from non-prescription remedies to mechanical stimulation of
the involved anatomical structures.
◊ Unfortunately, most of the evidence for treatments of hiccups come from uncontrolled observational
trials or case-control series or reports. Valid randomised trials are therefore needed to thoroughly
investigate the effectiveness of therapies for this indication.
Hiccups Basics
Definition
A hiccup is an abrupt contraction of the inspiratory muscles that repeats several times per minute. The
resultant sudden rush of air into the lungs causes the glottis to close, creating a distinctive 'hic' sound.
BASICS
Epidemiology
Benign hiccups are very common and affect all ages, including the fetus. Males are affected more than
females, with a ratio of 4:1. Persistent intractable hiccups are rare and affect males and females equally.
Hiccups of psychogenic origin are more common in females, while those originating from an organic
aetiology occur more commonly in males.[1]
Aetiology
The aetiology of hiccups is not fully understood.
Benign hiccups can be caused by gastric distension from aerophagia, excessive food and alcohol
consumption, and drinking carbonated beverages. Other causes include sudden changes in ambient or GI
temperature (e.g., cold showers, drinking hot or cold beverages), sudden excitement, and emotional stress.
Various underlying mechanisms can lead to persistent hiccups. Although more than 100 conditions have
been implicated, no causal relationships have been consistently shown. The causes of persistent hiccups
can be divided into 2 categories: psychogenic and organic. Persistent intractable hiccups should only be
classified as psychogenic after organic causes have been excluded.
• Peripheral processes involve irritation of the diaphragmatic, phrenic, and vagus nerves. Diaphragmatic
and phrenic nerve irritation may result from subphrenic abscess, splenomegaly, hepatomegaly,
myocardial infarction, pericarditis, a hiatus hernia, oesophageal cancer, or an aberrant cardiac
pacemaker electrode. Irritation of the vagus nerve may result from a foreign body irritating the
tympanic membrane, pharyngitis, laryngitis, a goitre or neck cyst, pneumonia, empyema, bronchitis,
asthma, pleuritis, oesophagitis, aortic aneurysm, tuberculosis, lung cancer, cor pulmonale,
mediastinitis, gastric atony, gastric cancer, gastritis, duodenal ulcer, pancreatitis, pancreatic cancer,
intra-abdominal abscess, bowel obstruction, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's
disease, gastrointestinal haemorrhage, appendicitis, hepatitis, or prostatic disease.[2] [3] [4] [5]
• Central processes include structural lesions (intracranial neoplasm, syringomyelia, multiple sclerosis,
ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or infarction, arterio-venous
malformation, vascular insufficiency), infection (meningitis, encephalitis, neurosyphilis, malaria, herpes
zoster), trauma, and epilepsy.[6] [7] [8]
• Metabolic causes include uraemia, diabetes mellitus, gout, hyponatraemia, hypocalcaemia,
hypokalaemia, and alkalosis. Electrolyte disturbances can decrease the central inhibition of the hiccup
reflex arc, leading to persistent intractable hiccups.
• Toxic causes include alcohol, dexamethasone, diazepam, sulfonamides, anti-epileptics, and alpha-
methyldopa.[9]
• Psychogenic disorders associated with the development of persistent intractable hiccups are
personality disorder, conversion reaction, hysterical neurosis, anorexia nervosa, sudden shock, and
grief reaction.[4] [10]
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Aug 24, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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Hiccups Basics
Hiccups associated with sedation or anaesthesia can be considered as a separate subtype. The hiccup
reflex is usually inhibited by the cortex, but during sedation and anaesthesia this inhibition is decreased,
leading to hiccups.[1] [11] [12]
BASICS
Pathophysiology
The exact mechanism underlying hiccups remains unknown. They can result from abnormalities of both
the central and peripheral nervous systems. The afferent limb of the hiccup reflex arc involves the phrenic
and vagus nerves, as well as the sympathetic chain. The primary efferent branch is the phrenic nerve;
however, efferent nerves to the glottis and accessory muscles (e.g., intercostals, scalenus muscles) are also
involved. The central connection is located between the third and fifth cervical segments. Following activation
of the hiccup reflex arc, an abrupt inspiration occurs. Hiccups usually involve unilateral diaphragmatic
contraction, frequently confined to the left hemi-diaphragm. Although bilateral contractions occur, one
side usually dominates.[12] The accelerated movement of air leads to a sudden closure of the glottis
approximately 35 milliseconds later. This cycle can repeat 4 to 60 times a minute. The arterial partial
pressure of carbon dioxide (PCO2) level has an impact on the frequency of hiccups. Increasing PCO2 levels
lower the frequency, whereas hyperventilation (leading to reduced CO2 levels) increases the number of
hiccups per minute.
Classification
Clinical classification
Benign hiccups
• Self-limiting with a duration of <1 hour and no associated complications.

Persistent intractable hiccups
• Not self-limiting and with a duration of up to several years. Associated with an underlying organic or
psychogenic cause, and associated complications may develop.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Aug 24, 2018.
5
Hiccups Prevention
Primary prevention
The development of benign hiccups can be averted by avoiding predisposing factors such as excessive food
or alcohol consumption, drinking carbonated beverages, sudden changes in ambient or gastrointestinal
temperature (e.g., cold showers, drinking hot or cold beverages), sudden excitement, and emotional stress.
There are no preventative strategies for the development of persistent intractable hiccups.[1] [11] [12]
Secondary prevention
The measures for the prevention of further episodes of benign hiccups are much the same as those
described for the primary prevention of such hiccups, with avoidance of known predisposing factors.
PREVENTION
Hiccups Diagnosis
Case history
Case history #1
A 27-year-old man presents with a 4-day history of persistent hiccups. The hiccups occur 4 to 6 times per
minute and persist during sleep. The patient complains that he is becoming progressively fatigued and
distressed by their persistence and frequency. No relief has been obtained from various home remedies.
The patient denies any other symptoms, has no significant past medical history, and is not taking any
regular medications. Examination of the right external auditory canal reveals a small hair in contact with
the tympanic membrane. The remainder of the physical examination is unremarkable. The hair is irrigated
from the canal, leading to an abrupt cessation of the hiccups. The hiccups do not recur.
Case history #2
A 43-year-old man presents with frequent hiccups that occur after drinking ice-cold carbonated
beverages. They normally last about 2 minutes and never longer than 15 minutes. The patient denies
any other symptoms. The patient has no significant past medical history, and the physical examination is
unremarkable. The patient is informed of the benign nature of the condition and is advised to avoid large
volumes of cold carbonated fluids.
Step-by-step diagnostic approach

The diagnosis of hiccups is clinical and derived primarily from a thorough clinical history. The underlying
cause of persistent intractable hiccups is identified through a focused history, physical examination, and
targeted investigations. Depending on the initial findings, referral to an appropriate specialist may be required
to direct further investigations and initiate treatment of any underlying condition.
Clinical history
DIAGNOSIS
The severity, duration, predisposing factors, and characteristics of the hiccups, as well as a description of
previous episodes, should be established. Hiccups are characterised by a distinctive 'hic' sound resulting
from sudden glottic closure interrupting an abrupt inhalation secondary to diaphragmatic spasm. The
duration and intensity of hiccups allows differentiation between benign self-limiting hiccups and persistent
intractable hiccups; those lasting >1 hour and associated with other symptoms and complications are
classified as persistent. Persistence of hiccups during sleep suggests an organic cause and may lead
to insomnia, with subsequent fatigue and exhaustion during the day.[11] This in turn leads to impaired
alertness and concentration, with consequences for work and social activities.
Predisposing factors include excessive food or alcohol consumption, drinking carbonated beverages,
sudden changes in ambient or gastrointestinal temperature (e.g., cold showers, drinking hot or cold
beverages), sudden excitement, and emotional stress.
A thorough past medical and drug history, as well as a systems review, should follow. It is important to
obtain information regarding conditions that can affect the hiccup reflex arc.
7
Hiccups Diagnosis
• Diaphragmatic and phrenic nerve irritation may result from subphrenic abscess, splenomegaly,
hepatomegaly, myocardial infarction, pericarditis, a hiatus hernia, oesophageal cancer, or an
aberrant cardiac pacemaker electrode.
• Irritation of the vagus nerve may result from a foreign body irritating the tympanic membrane,
pharyngitis, laryngitis, a goitre or neck cyst, pneumonia, empyema, bronchitis, asthma, pleuritis,
oesophagitis, aortic aneurysm, tuberculosis, lung cancer, cor pulmonale, mediastinitis, gastric
atony, gastric cancer, gastritis, duodenal ulcer, pancreatitis, pancreatic cancer, intra-abdominal
abscess, bowel obstruction, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's disease,
gastrointestinal haemorrhage, appendicitis, hepatitis, or prostatic disease.[2] [3] [4] [5]
• Central nervous system causes include structural lesions (intracranial neoplasm, syringomyelia,
multiple sclerosis, ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or
infarction, arterio-venous malformation, vascular insufficiency), infection (meningitis, encephalitis,
neurosyphilis, malaria, herpes zoster), trauma, and epilepsy.[6] [7] [8]
hypokalaemia, and alkalosis. Electrolyte disturbances can decrease the central inhibition of the
hiccup reflex arc, leading to persistent intractable hiccups.
Dyspnoea, cough, sputum, and pleuritic chest pain indicate possible pulmonary involvement.
Gastrointestinal involvement is indicated by such symptoms as abdominal pain, heartburn, vomiting,
diarrhoea, jaundice, dysphagia, and odynophagia. Seizures and peripheral sensory and motor symptoms
are indicative of possible central nervous system involvement. Fever, unexplained weight loss, and night
sweats may indicate an underlying malignancy such as oesophageal, lung, gastric, or pancreatic cancer.
The presence of chronic diseases such as diabetes mellitus, gout, and renal insufficiency should
be noted, and a detailed drug history should pay particular attention to dexamethasone, diazepam,
sulfonamides, anti-epileptics, and alpha-methyldopa. History of smoking, alcohol consumption, and
illicit drug use should be established. Psychological involvement is suggested by a history of personality
disorder, conversion reaction, hysterical neurosis, anorexia nervosa, a sudden shock, or a grief
reaction.[4] [10]
Physical examination
DIAGNOSIS
The physical examination in benign hiccups is unremarkable; however, it may reveal signs of the
underlying cause of persistent intractable hiccups.
There may be evidence of weight loss and malnutrition secondary to persistent intractable hiccups.
Assessment of the neck region may show evidence of trauma, or reveal a foreign body in the auditory
canal, nuchal rigidity, a goitre or neck cyst, cervical lymphadenopathy, or pharyngitis. Examination of
the respiratory system may reveal conditions such as asthma, pneumonia, empyema, tuberculosis,
or pleuritis. Abdominal examination may reveal splenomegaly, hepatomegaly, an abdominal aortic
aneurysm, or an acute abdomen (e.g., cholecystitis, cholelithiasis, pancreatitis, appendicitis, intestinal
obstruction, rupture of a hollow viscus). Neurological examination may show evidence of a stroke,
meningismus, encephalitis, or a space-occupying lesion.[11]
Laboratory investigations
A routine blood panel including full blood count, urea, and serum electrolytes should be undertaken in all
patients with persistent intractable hiccups. The selection of other laboratory tests such as liver function
tests, gamma glutamyl transpeptidase, C-reactive protein and erythrocyte sedimentation rate, serum
Hiccups Diagnosis
amylase, an arterial blood gas, and a toxicology screen (including blood alcohol) is dictated by the results
of the clinical history and physical examination.[1]
Investigation of the underlying cause

Further investigations to identify the underlying cause of persistent intractable hiccups are directed
by the clinical history, physical examination findings, and initial investigation results, and may include
assessment of conditions related to the cardiac, respiratory, gastrointestinal, and neurological systems.
A chest x-ray, pulmonary function tests, and ECG may be undertaken to identify pulmonary, mediastinal,
and cardiac aetiologies (e.g., myocardial infarction, pericarditis, an aberrant cardiac pacemaker electrode,
pneumonia, empyema, bronchitis, asthma, pleuritis, aortic aneurysm, tuberculosis, lung cancer, cor
pulmonale, and mediastinitis) capable of irritating the phrenic and vagus nerves, or the diaphragm
itself.[12]
Computed tomography (CT) or magnetic resonance imaging of the head and a lumbar puncture may
reveal neurological aetiologies, including structural lesions (intracranial neoplasm, syringomyelia, multiple
sclerosis, ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or infarction, arterio-
venous malformation, vascular insufficiency), infection (meningitis, encephalitis, neurosyphilis, malaria,
herpes zoster), and trauma.[6] [7] [8]
Endoscopy of the upper gastrointestinal tract and an abdominal CT may be undertaken to identify
gastrointestinal aetiologies such as oesophagitis, oesophageal cancer, duodenal ulcer, gastritis,
subphrenic abscess, splenomegaly, hepatomegaly, hiatus hernia, gastric cancer, pancreatitis, pancreatic
cancer, intra-abdominal abscess, bowel obstruction, abdominal aortic aneurysm, cholecystitis,
cholelithiasis, ulcerative colitis, Crohn's disease, gastrointestinal haemorrhage, appendicitis, and hepatitis.
Otoscopy and pharyngoscopy may reveal a foreign body irritating the tympanic membrane, or pharyngitis,
respectively.
Risk factors
DIAGNOSIS
Weak
aerophagia, temperature changes, and emotional states
• Factors known to predispose to benign hiccups are gastric distension from aerophagia, excessive food
and alcohol consumption, and drinking carbonated beverages.
• Other causes include sudden changes in ambient or gastrointestinal temperature (e.g., cold showers,
drinking hot or cold beverages), sudden excitement, and emotional stress.
diaphragmatic and phrenic nerve irritation

• Diaphragmatic and phrenic nerve irritation may result from subphrenic abscess, splenomegaly,
hepatomegaly, myocardial infarction, pericarditis, a hiatus hernia, oesophageal cancer, or an aberrant
cardiac pacemaker electrode.
vagus nerve irritation

• Irritation of the vagus nerve may result from a foreign body irritating the tympanic membrane,
pharyngitis, laryngitis, a goitre or neck cyst, pneumonia, empyema, bronchitis, asthma, pleuritis,
9
Hiccups Diagnosis
oesophagitis, aortic aneurysm, tuberculosis, lung cancer, cor pulmonale, mediastinitis, gastric atony,
gastric cancer, gastritis, duodenal ulcer, pancreatitis, pancreatic cancer, intra-abdominal abscess,
bowel obstruction, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's disease, gastrointestinal
haemorrhage, appendicitis, hepatitis, or prostatic disease.[2] [3] [4] [5]
central nervous system disorders

• Central processes include structural lesions (intracranial neoplasm, syringomyelia, multiple sclerosis,
ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or infarction, arterio-venous
malformation, vascular insufficiency), infection (meningitis, encephalitis, neurosyphilis, malaria, herpes
zoster), trauma, and epilepsy.[6] [7] [8]
metabolic/electrolyte abnormalities
hypokalaemia, and alkalosis. Electrolyte disturbances can decrease the central inhibition of the hiccup
reflex arc, leading to persistent intractable hiccups.
toxins/drugs
• Toxic causes include alcohol, dexamethasone, diazepam, sulfonamides, anti-epileptics, and alpha-
methyldopa.[9]
psychogenic disorders
• Include personality disorder, conversion reaction, hysterical neurosis, anorexia nervosa, sudden shock,
and grief reaction.[4] [10]
sedation or anaesthesia
• Considered as a separate subtype. The hiccup reflex is usually inhibited by the cortex, but during
sedation and anaesthesia this inhibition is decreased, leading to hiccups.[1] [11] [12]
History & examination factors

DIAGNOSIS
Key diagnostic factors

presence of risk factors (common)
• Predisposing factors for the development of benign hiccups include gastric distension from
aerophagia, excessive food and alcohol consumption, drinking carbonated beverages, sudden
changes in ambient or GI temperature (e.g., cold showers, drinking hot or cold beverages), sudden
excitement, and emotional stress. Underlying conditions that cause irritation of the diaphragmatic,
phrenic, and vagus nerves, CNS disease, metabolic disorders and electrolyte disturbances, toxins and
drugs, psychogenic disorders, as well as sedation and anaesthesia, may lead to persistent intractable
hiccups.
'hic' sound (common)

• Hiccups are characterised by a distinctive 'hic' sound resulting from sudden glottic closure interrupting
an abrupt inhalation secondary to diaphragmatic spasm.
Other diagnostic factors

duration <1 hour (benign hiccups) (common)
Hiccups Diagnosis
• Benign hiccups are self-limiting with no associated complications.
duration >1 hour (persistent intractable hiccups) (uncommon)

• Persistent intractable hiccups are not self-limiting and may last for several years. They are associated
with an underlying organic or psychogenic cause, which may include a wide range of conditions
related to cardiac, respiratory, gastrointestinal, or neurological conditions, and complications may
develop.
persistence during sleep (uncommon)

• This suggests an organic cause and may lead to insomnia, with subsequent fatigue and exhaustion
during the day.[11] This in turn leads to impaired alertness and concentration, with consequences for
work and social activities.
associated features of underlying cause (uncommon)

• Persistent intractable hiccups may be associated with symptoms and signs of the underlying cause.
weight loss and malnutrition (uncommon)

• Severe forms of persistent intractable hiccups can complicate eating and drinking. This may lead to
malnutrition and dehydration, with subsequent loss of weight. Weight loss is very common in patients
with hiccups.
• Weight loss may also be a sign of an underlying aetiology.
Diagnostic tests
1st test to order
Test Result
clinical diagnosis characteristic 'hic' sound;
• Diagnosis is clinical based on history and physical examination alone. duration and intensity
DIAGNOSIS
allows differentiation
between benign self-
limiting hiccups and
persistent intractable
hiccups
Other tests to consider
Test Result
FBC normal, or abnormal if
underlying cause
• Abnormal findings include leukocytosis in inflammation or infection,
and anaemia in malignancy or GI haemorrhage.
serum electrolytes normal, or abnormal if
underlying cause
• May reveal hyponatraemia, hypocalcaemia, or hypokalaemia.
• Electrolyte disturbances can decrease the central inhibition of the
hiccup reflex arc, leading to persistent intractable hiccups.
11
Hiccups Diagnosis
Test Result
urea normal, or abnormal if
underlying cause
• Urea is elevated in uraemia, which is a potential organic cause of
persistent intractable hiccups.
CRP and erythrocyte sedimentation rate normal, or abnormal if
underlying cause
• May be elevated in inflammation, infection, or malignancy.
• Several inflammatory and malignant conditions can lead to persistent
intractable hiccups.
liver function tests normal, or abnormal if
underlying cause
• Aspartate aminotransferase and alanine aminotransferase may be
elevated in hepatitis, and alkaline phosphatase may be elevated in
biliary obstruction.
• Hepatitis, cholecystitis, and cholelithiasis are potential organic causes
of persistent intractable hiccups.
gamma glutamyl transpeptidase (gamma-GT) normal, or abnormal if
underlying cause
• Gamma-GT may be elevated in biliary obstruction and chronic
alcoholism.
• Hepatitis, cholecystitis, and cholelithiasis are potential organic causes
of persistent intractable hiccups.
serum amylase normal, or abnormal if
underlying cause
• Elevated in pancreatitis, which is a potential organic cause of
toxicology screen normal, or abnormal if
underlying cause
• May reveal elevated blood alcohol, or positive drug screening for
tetrahydrocannabinol, amfetamines, cocaine, sedatives, tricyclics.
• Various toxins, including alcohol and certain illicit drugs, can lead to
arterial blood gas normal, or abnormal if
underlying cause
• Alkalosis is a potential organic cause of persistent intractable
DIAGNOSIS
hiccups.
ECG normal, or abnormal if
underlying cause
• May reveal evidence of ischaemia, pericarditis, a pacemaker, or
electrolyte disturbances.
• Myocardial infarction, pericarditis, an aberrant cardiac pacemaker
electrode, and electrolyte disturbances (hyponatraemia,
hypocalcaemia, or hypokalaemia) are potential organic causes of
CXR normal, or abnormal if
underlying cause
• May reveal evidence of pulmonary disease, neoplasm, mediastinal
lymphadenopathy, cardiac abnormality, or pacemaker.
• Diaphragmatic and phrenic nerve irritation leads to persistent
intractable hiccups and may result from pericarditis, or from an
aberrant cardiac pacemaker electrode. Irritation of the vagus nerve
may result from pneumonia, empyema, bronchitis, asthma, pleuritis,
aortic aneurysm, tuberculosis, lung cancer, cor pulmonale, and
mediastinitis, leading to persistent intractable hiccups.[2] [3] [4] [5]
Hiccups Diagnosis
Test Result
pulmonary function tests normal, or abnormal if
underlying cause
• May reveal an obstructive or restrictive pulmonary disorder.
• Several obstructive and restrictive pulmonary conditions, including
asthma, pneumonia, pleuritis, and empyema, are potential organic
causes of persistent intractable hiccups.
CT abdomen normal, or abnormal if
underlying cause
• May reveal evidence of obstruction, perforation, inflammation,
abscess, neoplasm, hepatosplenomegaly, or abdominal aortic
aneurysm.
• Diaphragmatic and phrenic nerve irritation leads to persistent
intractable hiccups and may result from several intra-abdominal
pathologies including subphrenic abscess, splenomegaly,
hepatomegaly, and a hiatus hernia. Irritation of the vagus nerve may
result from gastric cancer, duodenal ulcer, pancreatitis, pancreatic
cancer, intra-abdominal abscess, bowel obstruction, abdominal aortic
aneurysm, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's
disease, gastrointestinal haemorrhage, appendicitis, and hepatitis,
leading to persistent intractable hiccups.[2] [3] [4] [5]
endoscopy of the upper gastrointestinal tract normal, or abnormal if
underlying cause
• May reveal evidence of oesophagitis, oesophageal cancer, duodenal
ulcer, or gastritis.
• These conditions may cause irritation of the phrenic and vagus
nerves, leading to persistent intractable hiccups.
CT or MRI head normal, or abnormal if
underlying cause
• May reveal evidence of a space-occupying lesion, inflammation,
haemorrhage, or infarction.
• Central processes leading to persistent intractable hiccups include
structural lesions (intracranial neoplasm, syringomyelia, multiple
sclerosis, ventriculo-peritoneal shunt), vascular lesions (intracranial
haemorrhage or infarction, arterio-venous malformation, vascular
insufficiency), infection (meningitis, encephalitis, neurosyphilis,
DIAGNOSIS
malaria, herpes zoster), and trauma.[6] [7] [8]
lumbar puncture normal, or abnormal if
• May reveal elevated protein, decreased glucose, leukocytes, bacteria, underlying cause
or xanthochromic liquor.
• Meningitis, encephalitis, and intracranial haemorrhage are potential
organic causes of persistent intractable hiccups.
otoscopy normal, or abnormal if
underlying cause
• May reveal tympanic membrane irritation.
• Irritation of the vagus nerve may result from a foreign body irritating
the tympanic membrane, leading to persistent intractable hiccups.
pharyngoscopy normal, or abnormal if
underlying cause
• May reveal inflammation of the pharyngeal mucosa.
• Pharyngitis may cause irritation of the vagus nerve, leading to
13
Hiccups Diagnosis
Differential diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Gasping • A convulsive or laborious • Clinical diagnosis with no
respiration with an differentiating tests.
abnormal breathing pattern
characterised by shallow,
slow (3 to 4 per minute),
and irregular inspirations
followed by irregular pauses.
The distinctive 'hic' noise
produced by closure of the
glottis in hiccups is absent.
Burping • A noisy expulsion of gas • Clinical diagnosis with no

from the stomach through differentiating tests.
the mouth, with absence of
the involuntary inspiration
observed in hiccups.
Diagnostic criteria
Clinical criteria
Benign hiccups
• Self-limiting, with a duration of <1 hour and no associated complications.
Persistent intractable hiccups
• Not self-limiting and with a duration of up to several years. Associated with an underlying organic or
DIAGNOSIS
psychogenic cause, and associated complications may develop.
Hiccups Treatment
Step-by-step treatment approach

In most patients, hiccups are benign and self-limiting or cured with simple home remedies and do not
require any medical intervention. Pharmacological and more invasive treatments should be reserved for the
rare patients who have persistent intractable hiccups, for symptomatic relief and for avoidance of potential
complications. Treatment should be guided by the duration and intensity of the hiccups and initiated by a
specialist physician. The associated risks of invasive treatment should be weighed against the foreseen
benefits, to avoid a generally benign condition resulting in serious, treatment-related complications.
Factors known to predispose to hiccups, such as excessive food or alcohol consumption, drinking carbonated
beverages, sudden changes in ambient or gastrointestinal temperature (e.g., cold showers, drinking hot or
cold beverages), sudden excitement, and emotional stress, should be avoided in all patients.
Valid scientific data regarding the treatment of hiccups are difficult to find.[13] The vast majority of evidence
for treatments of hiccups has come from uncontrolled observational trials or case-control series or reports.
Valid randomised placebo-controlled trials are therefore needed to thoroughly investigate the benefits and
harms of interventions for this indication.
Home remedies
Several home remedies, used alone or in combination, are usually effective in curing episodes of benign
hiccups. These include breath holding, the Valsalva manoeuvre (a forced expiration against a closed
glottis), breathing into a paper bag, pulling on the tongue, sneezing, swallowing a teaspoon of granulated
sugar, sipping iced water, compressing the diaphragm by pulling the knees up to the chest, swallowing
large amounts of water while closing the nose and ears, and a sudden fright.
Treatment of underlying cause

Successful treatment of the underlying cause of persistent intractable hiccups may lead to termination
of these hiccups.[14] If hiccups persist despite specific therapy, physical manipulation should be
attempted.[15]
Physical manipulation
Interruption of the hiccup reflex arc leads to termination of hiccups and can be achieved through several
techniques. Stimulation of the nasopharynx with a finger, rubber catheter, or cotton-tipped applicator,
lifting the uvula, or inducing a gasp by smelling salts or other noxious agents can be tried.
Second-line techniques include instilling ammonia or ether into the nasopharynx, carotid sinus massage,
applying supraorbital pressure, digital compression to the root of the neck over the course of the
phrenic nerve, and compression of the thyroid cartilage. These procedures are not without risk. Vagal
manoeuvres can lead to severe bradycardia, and the application of noxious agents can cause local
adverse effects such as corrosion.
Nasogastric aspiration and manipulation of the auditory canal can also be employed. Treatment of
hiccups with digital rectal massage and sexual intercourse is also well documented.[16] [17]
TREATMENT
As physical manipulation techniques are associated with potential harmful effects, they should only be
attempted once less invasive measures have failed.
15
Hiccups Treatment
Pharmacotherapy
Persistent intractable hiccups unresponsive to physical manipulation often require pharmacological
therapy. Chlorpromazine is the recommended drug of choice. If it proves successful in terminating the
hiccups, oral chlorpromazine at the same dose can be continued for 7 to 10 days. In the case of treatment
failure, metoclopramide can be tried. It should be used for up to 5 days only, in order to minimise the risk
of neurological and other adverse effects.[18] Its use for this indication is off-label and it should be used
with caution. Quinidine, phenytoin, or valproic acid are alternative agents. Valproate and its analogues
are contraindicated during pregnancy due to the risk of congenital malformations and developmental
problems in the infant/child. In both Europe and the US, valproate and its analogues must not be used in
female patients of childbearing potential unless there is a pregnancy prevention programme in place and
certain conditions are met.[19]
Various other drugs have also been used with some success, although relevant double-blind studies
have not shown any increased benefits with using these agents.[11] [20] [21] [22] The use of baclofen (a
gamma-aminobutyric acid analogue), haloperidol, nifedipine, gabapentin,[23] [24] and antidepressants
(i.e., amitriptyline and sertraline) can be found in the literature. The inhalation of 5% carbon dioxide has
also been described.
Alternative therapies
In addition to conventional physical manipulation techniques and pharmacotherapy, alternative therapies
such as acupuncture,[25] hypnosis, and psychotherapy can be tried for persistent intractable hiccups.[1]
[17]
Invasive therapy
In refractory hiccups associated with significant discomfort and morbidity, disruption of the phrenic
nerve (i.e., the efferent branch of the hiccup reflex arc) may be considered. Permanent phrenic nerve
crush or transection should be preceded by a nerve block with a long-acting local anaesthetic. Before
treatment, which leaflet of the diaphragm is contracting has to be established, and the phrenic nerve
responsible for the unilateral contraction must be identified clearly by means of nerve stimulation. As
serious impairment of pulmonary function can occur after diaphragmatic paralysis, this procedure is only
justified in extreme cases, and all other possible conservative treatments, including alternative therapies,
should be exhausted before embarking on phrenic nerve disruption.[1] [17]
Treatment details overview

Consult your local pharmaceutical database for comprehensive drug information including contraindications,
drug interactions, and alternative dosing. ( see Disclaimer )
Acute ( summary )
benign hiccups
1st home remedies

TREATMENT
plus avoidance of precipitating factors
Ongoing ( summary )
Hiccups Treatment
Ongoing ( summary )
persistent intractable hiccups
1st treatment of underlying cause
2nd physical manipulation
adjunct alternative therapies
3rd pharmacotherapy
4th phrenic nerve disruption
TREATMENT
17
Hiccups Treatment
Treatment options
Acute
benign hiccups
1st home remedies
» Several home remedies, used alone or in

combination, are usually effective in curing
episodes of benign hiccups.
» These include breath holding, the Valsalva

manoeuvre (a forced expiration against a
closed glottis), breathing into a paper bag,
pulling on the tongue, sneezing, swallowing a
teaspoon of granulated sugar, sipping iced water,
compressing the diaphragm by pulling the knees
up to the chest, swallowing large amounts of
water while closing the nose and ears, and a
sudden fright.
plus avoidance of precipitating factors
» Factors known to predispose to hiccups, such

as excessive food or alcohol consumption,
drinking carbonated beverages, sudden changes
in ambient or gastrointestinal temperature (e.g.,
cold showers, drinking hot or cold beverages),
sudden excitement, and emotional stress, should
be avoided.
Ongoing
persistent intractable hiccups
1st treatment of underlying cause
» Successful treatment of the underlying cause

of persistent intractable hiccups may lead to
termination of these hiccups.[14] If hiccups
persist despite specific therapy, physical
manipulation should be attempted.[15]
2nd physical manipulation
» Interruption of the hiccup reflex arc leads to

termination of hiccups and can be achieved
through several techniques. Stimulation of the
nasopharynx with a finger, rubber catheter,
or cotton-tipped applicator, lifting the uvula,
or inducing a gasp by smelling salts or other
noxious agents can be tried.
TREATMENT
» Second-line techniques include instilling

ammonia or ether into the nasopharynx,
carotid sinus massage, applying supraorbital
pressure, digital compression to the root of
the neck over the course of the phrenic nerve,
Hiccups Treatment
Ongoing
and compression of the thyroid cartilage.
These procedures are not without risk. Vagal
manoeuvres can lead to severe bradycardia,
and the application of noxious agents can cause
local adverse effects such as corrosion.
» Nasogastric aspiration and manipulation of the

auditory canal can also be employed. Treatment
of hiccups with digital rectal massage and sexual
intercourse is also well documented.[16] [17]
» As physical manipulation techniques are

associated with potential harmful effects, they
should only be attempted once less-invasive
measures have failed.
» In addition to conventional physical

manipulation techniques, alternative therapies
such as acupuncture,[25] hypnosis, and
psychotherapy can be tried for persistent
intractable hiccups.[1] [17]
3rd pharmacotherapy
Primary options
» chlorpromazine: 25-50 mg intravenously

every 6 hours initially, followed by 25-50 mg
orally four times daily for 7-10 days
Secondary options
» metoclopramide: 10 mg intravenously every

8 hours for a maximum of 5 days, maximum
30 mg/day
OR
» quinidine sulfate: 200 mg orally four times

daily
OR
» phenytoin: 200 mg intravenously initially,

followed by 100 mg orally four times daily
OR
» valproic acid: 15 mg/kg/day orally
Tertiary options
TREATMENT
» baclofen: 5-10 mg orally three times daily
OR
19
Hiccups Treatment
Ongoing
» haloperidol: 2-5 mg intramuscularly once
daily
OR
» nifedipine: 10-20 mg orally (immediate-

release) three times daily
OR
» amitriptyline: 10 mg orally three times daily
OR
» gabapentin: 100 mg orally three times daily

initially, increase according to response,
maximum 900 mg/day
OR
» sertraline: 50 mg orally once daily
OR
» carbon dioxide: (5%) consult specialist for

guidance on dose
» Persistent intractable hiccups unresponsive

to physical manipulation often require
pharmacological therapy.
» Chlorpromazine is the recommended drug of

choice. If it proves successful in terminating the
hiccups, oral chlorpromazine at the same dose
can be continued for 7 to 10 days.
» In the case of treatment failure,

metoclopramide can be tried. It should be used
for up to 5 days only, in order to minimise the risk
of neurological and other adverse effects.[18] Its
use for this indication is off-label and it should
be used with caution. Quinidine, phenytoin, or
valproic acid are alternative agents.
» Valproate and its analogues are

contraindicated during pregnancy due to the risk
of congenital malformations and developmental
problems in the infant/child. In both Europe
and the US, valproate and its analogues must
not be used in female patients of childbearing
TREATMENT
potential unless there is a pregnancy prevention

programme in place and certain conditions are
met.[19]
» Various other drugs have also been used

with some success, although relevant double-
Hiccups Treatment
Ongoing
blind studies have not shown any increased
benefits with using these agents.[11] [20] [21]
[22] The use of baclofen (a gamma-aminobutyric
acid analogue), haloperidol, nifedipine,
gabapentin,[23] [24] and antidepressants (i.e.,
amitriptyline and sertraline) can be found in the
literature. The inhalation of 5% carbon dioxide
has also been described.
» In addition to conventional physical

manipulation techniques and pharmacotherapy,
alternative therapies such as acupuncture,
hypnosis, and psychotherapy can be tried as
possible conservative treatments for persistent
intractable hiccups.[1] [17]
4th phrenic nerve disruption
» In refractory hiccups associated with significant

discomfort and morbidity, disruption of the
phrenic nerve (i.e., the efferent branch of the
hiccup reflex arc) may be considered.
» Permanent phrenic nerve crush or transection

should be preceded by a nerve block with a
long-acting local anaesthetic. Before treatment,
which leaflet of the diaphragm is contracting
has to be established, and the phrenic nerve
responsible for the unilateral contraction must be
identified clearly by means of nerve stimulation.
» As serious impairment of pulmonary function

can occur after diaphragmatic paralysis, this
procedure is only justified in extreme cases,
and all other possible conservative treatments,
including alternative therapies, should be
exhausted before embarking on phrenic nerve
disruption.[1] [17]
TREATMENT
21
Hiccups Follow up
Recommendations
Monitoring
FOLLOW UP
Depending on the severity of the persistent intractable hiccups, follow-up examinations should be
considered to avoid complications, although there are no specific methods of monitoring.
Patient instructions
In benign hiccups, patients should be reassured that the condition is most probably harmless and self-
limiting without the need for any medical attention. In persistent intractable hiccups, patients should be
warned of the possible complications (e.g., cardiac arrhythmias, insomnia, weight loss, and oesophagitis)
and instructed to look out for these.
Complications
Complications Timeframe Likelihood

interference with ventilation short term medium
Severe hiccups can interfere with ventilation in anaesthetised and ventilated patients. This is often seen
with the use of a laryngeal mask airway. Hiccups in intubated infants can lead to hyperventilation and
subsequent respiratory alkalosis.[26]
interference with medical procedures short term medium
Severe forms of hiccups during surgery, endoscopy, or imaging can jeopardise the quality of the
procedure.
In the rare situation where hiccups cause a sudden interference with a medical procedure or imaging
study (endoscopy, surgery, computed tomographic scan, magnetic resonance imaging), the patient can
be anaesthetised with either a volatile or non-volatile anaesthetic to achieve deeper sedation. If this is
unsuccessful, neuromuscular blocking agents (e.g., vecuronium) and mechanical ventilation can be used
to arrest the symptom. After the effects of the neuromuscular blocker wear off, the hiccups often return,
and it should be noted that anaesthesia and securing the airway (e.g., with a laryngeal mask airway) may
not be beneficial and may even cause a worsening of symptoms.[26] [27]
wound dehiscence short term low
Hiccups in the postoperative period do not only cause discomfort but can also lead to wound dehiscence
and insufficiency at the site of an anastomosis.
weight loss long term low
Severe forms of persistent intractable hiccups can complicate eating and drinking. This may lead to
malnutrition and dehydration, with subsequent loss of weight. Weight loss is not uncommon in patients
with persistent intractable hiccups.
oesophagitis long term low
Hiccups Follow up
Complications Timeframe Likelihood

Hiccups can result in reflux, leading to oesophagitis. Persistent reflux worsens the symptoms of
FOLLOW UP
oesophagitis, which is itself a cause of persistent intractable hiccups. Thus, a vicious cycle is created that
must be interrupted.
cardiac arrhythmias variable low
Supraventricular and ventricular arrhythmias can result from severe diaphragmatic contractions. It should
be noted that some underlying conditions can lead to both cardiac arrhythmias and hiccups.
insomnia variable low
Hiccups may keep the individual from sleeping, leading to fatigue and exhaustion during the day. Alertness
and concentration are impaired, with consequences for work and social activities. Constant stimulation of
the sympatho-adrenergic system may lead to adverse effects on the cardiovascular system.
Prognosis
Benign hiccups can be annoying or sometimes socially embarrassing, but they are rarely of clinical
significance.
Persistent intractable hiccups can last for several years. The intensity of the hiccups varies from mild
discomfort to a clinically significant malady. Reports indicate that there may be a sudden and unexpected
termination of persistent hiccups, even after years.
23
GUIDELINES Hiccups Guidelines
Hiccups References
Key articles
• Lewis JH. Hiccups: causes and cures. J Clin Gastroenterol. 1985 Dec;7(6):539-52. Abstract
REFERENCES
• Wagner MS, Stapczynski JS. Persistent hiccups. Ann Emerg Med. 1982 Jan;11(1):24-6. Abstract
• Rousseau P. Hiccups. South Med J. 1995 Feb;88(2):175-81. Abstract
• Zhu LL, Wang WX, Guo XG. Acupuncture for hiccups after stroke: a systematic review. Chin J Evid
Based Med. 2011;11:325-8.
References
1. Lewis JH. Hiccups: causes and cures. J Clin Gastroenterol. 1985 Dec;7(6):539-52. Abstract
2. Slipman CW, Shin CH, Patel RK, et al. Persistent hiccup associated with thoracic epidural injection.
Am J Phys Med Rehabil. 2001 Aug;80(8):618-21. Abstract
3. Smith HS, Busracamwongs A. Management of hiccups in the palliative care population. Am J Hosp
Palliat Care. 2003 Mar-Apr;20(2):149-54. Abstract
4. Reiss M, Reiss G. Singultus: indication of an atypical myocardial infarct? [in German] MMW Fortschr
Med. 2006 Mar 9;148(10):55-6. Abstract
5. Khorakiwala T, Arain R, Mulsow J, et al. Hiccups: an unrecognized symptom of esophageal cancer?

Am J Gastroenterol. 2008 Mar;103(3):801. Abstract
6. Nagayama T, Kaji M, Hirano H, et al. Intractable hiccups as a presenting symptom of cerebellar

hemangioblastoma: case report. J Neurosurg. 2004 Jun;100(6):1107-10. Abstract
7. Ruan X, Couch JP, Shah R, et al. Persistent hiccup associated with intrathecal morphine infusion
pump therapy. Am J Phys Med Rehabil. 2007 Dec;86(12):1019-22. Abstract
8. Homer JR, Davies JM, Amundsen LB. Persistent hiccups after attempted interscalene brachial plexus
block. Reg Anesth Pain Med. 2005 Nov-Dec;30(6):574-6. Abstract
9. Redondo-Cerezo E, Viñuelas-Chicano M, Pérez-Vigara G, et al. A patient with persistent hiccups and

gastro-oesophageal reflux disease. Gut. 2008 Jun;57(6):763, 771. Abstract
10. Sugimoto T, Takeda N, Yamakawa I, et al. Intractable hiccup associated with aseptic meningitis in a
patient with systemic lupus erythematosus. Lupus. 2008 Feb;17(2):152-3. Abstract
11. Wagner MS, Stapczynski JS. Persistent hiccups. Ann Emerg Med. 1982 Jan;11(1):24-6. Abstract
12. Rousseau P. Hiccups. South Med J. 1995 Feb;88(2):175-81. Abstract
25
Hiccups References
13. Moretto EN, Wee B, Wiffen PJ, et al. Interventions for treating persistent and intractable hiccups in
adults. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD008768. Full text Abstract
REFERENCES
14. Calsina-Berna A, García-Gómez G, González-Barboteo J, et al. Treatment of chronic hiccups in

cancer patients: a systematic review. J Palliat Med. 2012 Oct;15(10):1142-50. Abstract
15. Seyama H, Kurita H, Noguchi A, et al. Resolution of intractable hiccups caused by cerebellar
hemangioblastoma. Neurology. 2001 Dec 11;57(11):2142. Abstract
16. Peleg R, Peleg A. Case report: sexual intercourse as potential treatment for intractable hiccups. Can
Fam Physician. 2000 Aug;46:1631-2. Full text Abstract
17. Payne BR, Tiel RL, Payne MS, et al. Vagus nerve stimulation for chronic intractable hiccups: case
report. J Neurosurg. 2005 May;102(5):935-7. Abstract
18. European Medicines Agency. European Medicines Agency recommends changes to the use of
metoclopramide. July 2013 [internet publication]. Full text
19. European Medicines Agency. New measures to avoid valproate exposure in pregnancy endorsed.
March 2018 [internet publication]. Full text
20. Hernández JL, Pajarón M, García-Regata O, et al. Gabapentin for intractable hiccup. Am J Med. 2004
Aug 15;117(4):279-81. Abstract
21. Alonso-Navarro H, Rubio L, Jiménez-Jiménez FJ. Refractory hiccup: successful treatment with
gabapentin. Clin Neuropharmacol. 2007 May-Jun;30(3):186-7. Abstract
22. Hung YM, Miller MA, Patel MM. Persistent hiccups associated with intravenous corticosteroid therapy.
J Clin Rheumatol. 2003 Oct;9(5):306-9. Abstract
23. Palacio Lacambra ME, Juárez Giménez JC, Peña MJ, et al. Medication and singultus [in Spanish].
Atencion Farmaceutica. 2011;13:18-23.
24. Thompson DF, Brooks KG. Gabapentin therapy of hiccups. Ann Pharmacother. 2013
Jun;47(6):897-903. Abstract
25. Zhu LL, Wang WX, Guo XG. Acupuncture for hiccups after stroke: a systematic review. Chin J Evid
Based Med. 2011;11:325-8.
26. Kranke P, Eberhart LH, Morin AM, et al. Treatment of hiccup during general anaesthesia or sedation: a
qualitative systematic review. Eur J Anaesthesiol. 2003 Mar;20(3):239-44. Abstract
27. Szibor-Kriesen U, Devide A, Hoetzel A, et al. Persistent intractable hiccup in the perioperative period
[in German]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2008 Oct;43(10):674-6. Abstract
Hiccups Disclaimer
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Publishing Group Ltd ("BMJ Group") tries to ensure that the information provided is accurate and up-to-
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This information is not intended to cover all possible diagnosis methods, treatments, follow up, drugs and
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27
Contributors:
// Authors:
Peter Kranke, MD, PhD, MBA

Professor of Anaesthesia
Department of Anaesthesia and Critical Care, University of Würzburg Hospital, Würzburg, Germany
DISCLOSURES: PK is an author of a reference cited in this topic.
Yvonne Jelting, MD
Assistant Physician and Study Subinvestigator
Department of Anesthesia and Critical Care, University Hospital of Wuerzburg, Wuerzburg, Germany
DISCLOSURES: YJ declares that she has no competing interests.
// Acknowledgements:
Professor Peter Kranke and Dr Yvonne Jelting would like to gratefully acknowledge Dr Thomas M.
Metterlein, a previous contributor to this topic. TMM declares that he has no competing interests.
// Peer Reviewers:
Andy Smith, BM, BS, MRCP, FRCA

Consultant Anaesthetist and Associate Director of Research and Development
Director, Lancaster Patient Safety Research Unit, Royal Lancaster Infirmary, Lancaster, UK
DISCLOSURES: AS declares that he has no competing interests.
Stefan K. Burgdorf, MD
Registrar
Department of Surgical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark
DISCLOSURES: SKB declares that he has no competing interests.
Howard Smith, MD, FACP

Academic Director of Pain Management
Associate Professor of Anesthesiology, Department of Anesthesiology, Albany Medical College, Albany, NY
DISCLOSURES: HS is an author of a reference cited in this topic.

Hiccups: The Right Clinical Information, Right Where It's Needed

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Hiccups

The right clinical information, right where it's needed

Last updated: Aug 24, 2018

◊ Hiccups is a common and mostly harmless condition.

• Self-limiting with a duration of <1 hour and no associated complications.

Step-by-step diagnostic approach

Investigation of the underlying cause

diaphragmatic and phrenic nerve irritation

vagus nerve irritation

central nervous system disorders

History & examination factors

Key diagnostic factors

'hic' sound (common)

Other diagnostic factors

duration >1 hour (persistent intractable hiccups) (uncommon)

persistence during sleep (uncommon)

associated features of underlying cause (uncommon)

weight loss and malnutrition (uncommon)

Other tests to consider

Condition Differentiating signs / Differentiating tests

Burping • A noisy expulsion of gas • Clinical diagnosis with no

• Self-limiting, with a duration of <1 hour and no associated complications.

Persistent intractable hiccups

psychogenic cause, and associated complications may develop.

Step-by-step treatment approach

Treatment of underlying cause

Treatment details overview

1st home remedies

plus avoidance of precipitating factors

1st treatment of underlying cause

2nd physical manipulation

adjunct alternative therapies

adjunct alternative therapies

4th phrenic nerve disruption

1st home remedies

» Several home remedies, used alone or in

» These include breath holding, the Valsalva

» Factors known to predispose to hiccups, such

1st treatment of underlying cause

» Successful treatment of the underlying cause

» Interruption of the hiccup reflex arc leads to

» Second-line techniques include instilling

» Nasogastric aspiration and manipulation of the

» As physical manipulation techniques are

» In addition to conventional physical

» chlorpromazine: 25-50 mg intravenously

» metoclopramide: 10 mg intravenously every

» quinidine sulfate: 200 mg orally four times

» phenytoin: 200 mg intravenously initially,

» valproic acid: 15 mg/kg/day orally

» baclofen: 5-10 mg orally three times daily

» nifedipine: 10-20 mg orally (immediate-

» amitriptyline: 10 mg orally three times daily

» gabapentin: 100 mg orally three times daily

» sertraline: 50 mg orally once daily

» carbon dioxide: (5%) consult specialist for

» Persistent intractable hiccups unresponsive

» Chlorpromazine is the recommended drug of

» In the case of treatment failure,

» Valproate and its analogues are

potential unless there is a pregnancy prevention

» Various other drugs have also been used

» In addition to conventional physical