Hiccups

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. ^{[2, 3]} Hiccups lasting longer than 1 month are termed intractable. The longest recorded attack of hiccups lasted for 6 decades.

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. ^[4] Typically, this is fewer than four 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 to T12

• 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

The cause of hiccups in children and infants is rarely found. Brief episodes in adults are usually benign and self-limiting. Typical causes include the following:

• Gastric distention (ie, from food, alcohol, or air)

• Sudden changes in ambient or gastric temperature

• Use of alcohol or tobacco in excess

Psychogenic causes (ie, excitement and stress) also may elicit hiccups.

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. ^{[2, 3]}

Male predominance exists in patients with non–central nervous system (CNS)-related hiccups and those of unknown origin. ^[5] About 82% of persistent or intractable episodes also 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. ^[6] Psychogenic conditions associated with hiccups include the following:

• Hysteria

• Shock

• Fear

• Personality disorders

• Conversion disorders

• Malingering

CNS-related causes of hiccups include the following:

• Structural lesions ^{[7, 8]} : 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

• Myocardial ischemia ^[9]

• 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 ^[10]

• Thoracic branches: Infection, tumors, ^[11] esophagitis (ie, reflux), myocardial infarction (MI), ^[12]  asthma, trauma, thoracic aortic aneurysm, or pacemaker lead complications ^[13]

• Abdominal branches: Tumors, ^[14] gastric distention, peptic ulcer, abdominal aortic aneurysm, infection, organ enlargement, or inflammation (eg, appendicitis, cholecystitis, pancreatitis, ^[15] or inflammatory bowel disease)

Procedure- or anesthesia-related causes of hiccups include the following ^{[16, 17]} :

• 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

• Hyperglycemia

• Uremia

• Hypocarbia

• Fever

Drugs associated with hiccups include the following:

• Benzodiazepines ^[18]

• Short-acting barbiturates

• Donepezil ^[19]

• Dexamethasone

• Alpha-methyldopa

Hiccups can occur at any age. They may even be observed in utero; preterm infants spend up to 2.5% of their time hiccupping. ^[20] 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 appears to be the same in males as it is in females; however, protracted and intractable hiccups occur more frequently in men (82% of cases).

A review of the literature (1990-2013) comprising 318 studies found a male predominance in hiccup patients, particularly when the causes were not related to the central nervous system or were unknown. ^[5]

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