Singultus

 Introduction

Singultus, more commonly known as hiccups, is a pervasive problem. Hiccups spare no population and have been observed in human beings from preterm infants to adults. Hiccups also occur in other mammals. Hiccups appear to serve no particular function and may be remnants of a primitive reflex.

Hiccups are often classified by the duration of the episodes. Hiccup bouts are acute episodes that terminate within 48 hrs. Hiccups lasting >48 hrs but <1 mo are identified as persistent hiccups, and those unfortunate enough to be afflicted with hiccups for >1 mo are identified as having intractable hiccups.

The frequency of hiccups numbers between 4 and 60 hiccups/min. Increased frequency of hiccups is noted with falls in PaCO₂. Transient hiccups tend to occur at night, and intractable hiccups tend to predominate in men. Although the majority of hiccups are benign, chronic hiccups may portend more ominous pathology.

Pathophysiology

Hiccups are believed to result from the stimulation of a hiccup reflex arc that involves both central and peripheral components. The afferent limb is composed of the phrenic nerve, vagus nerve, and sympathetic chain from T6 to T12. The efferent limb includes multiple brainstem and midbrain areas interacting with the motor fibers of the phrenic nerve. Within cervical spinous processes C3-C5, a central connection between afferent and efferent limbs exists. These interactions then manifest as repetitive, involuntary contractions of intercostal and diaphragmatic muscles with glottic closure resulting in the familiar of hiccup. Irritation in any component of this reflex arc may result in hiccups. Hiccups more commonly involve unilateral diaphragmatic contraction.

Etiology

The multiple components of the hiccup reflex arc allow for broad susceptibility to structural, inflammatory, infectious, or metabolic disturbances. More than 100 causes of hiccups have been described (Table ).

Benign transient hiccups are believed to arise from such common occurrences as gastric distention, aerophagia, tobacco use, sudden excitement or stress, or sudden changes in environmental or internal temperatures.

Chronic hiccups are often pathologic in nature and can be broadly classified into organic, psychogenic, medication induced, and miscellaneous origins. Central processes include any disruption of the brainstem or midbrain areas. Peripheral nervous system etiologies include those that irritate the vagus or phrenic nerves anywhere along their courses, including their cranial (vagus), cervical, thoracic, or abdominal portions.

TABLE . CAUSES OF HICCUPS

Organic Central

Vascular: ischemic/hemorrhagic strokes, arteriovenous malformations, head trauma lesions, vasculitis

Infections: encephalitis/meningitis, brain abscess, neurosyphilis

Structural: mass lesions

Peripheral

Meningeal/pharyngeal afferents: meningitis/laryngitis/abscess, goiters/cysts/tumors

Auricular afferents: foreign body

Thoracic afferents: chest trauma, neoplasm of lung, lymphadenopathy, myocardial infarction, pulmonary edema, pericarditis/pleuritis/esophagitis, aortic aneurysm, asthma/bronchitis/pneumonia, esophagitis/stricture/hernia, achalasia

Abdominal afferents: gastric distention, gastritis/hepatitis, peptic ulcers, pancreatic/biliary disease, bowel obstruction, appendicitis, inflammatory bowel disease, intraabdominal surgery, genitourinary disorders, direct diaphragmatic irritation

Psychogenic: stress/excitement, conversion/grief reactions, anorexia nervosa, malingering

Medications: steroids, barbiturates, benzodiazepines, alpha-blockers, dopaminergic agonists, antibiotics, nonsteroidal antiinflammatory

Miscellaneous: idiopathic, toxic/metabolic causes, alcohol, tobacco, sepsis, electrolyte abnormalities (sodium/calcium/potassium), uremia, diabetes mellitus Evaluation A detailed history and physical exam are critical to clarifying the etiology of hiccups. The onset, severity, and duration of hiccups are useful details. For example, hiccups occurring during sleep often point to an organic cause. A careful review of systems allows further assessment of the clinical impact of hiccups. Chronic persistent hiccups have been associated with such complications as malnutrition, fatigue, dehydration, cardiac arrhythmias, and insomnia. Social history also provides helpful diagnostic clues, as excessive alcohol and tobacco use can cause hiccups. Medications need to be discussed, as a number of medicines are known to precipitate hiccups (see Table). The physical exam allows further investigation into the cause of the patient's hiccups. A thorough exam of the head and neck allows for a search for masses, foreign bodies, or evidence of infection, which may be culprits in inducing hiccups. Lymphadenopathy may cause compression of neural structures and merit more intensive investigation for underlying pathologies. Given the extensive number of thoracic causes of hiccups, the chest exam is also crucial to identifying the underlying diagnosis and can shed light on underlying processes such as pneumonia or asthma. The physical exam should also include a careful neurologic assessment, because strokes and various neurologic disorders such as multiple sclerosis can often manifest with hiccups. No one lab study can diagnose hiccups. However, based on suspected etiologies from the history and physical exam, specific lab studies may be helpful. Specific tests such as serum alcohol or electrolyte levels can exclude metabolic and toxic causes of persistent hiccups. The chest radiograph can be helpful for ruling out cardiac, pulmonary, and mediastinal sources of peripheral nerve irritation. More specialized tests such as electroencephalogram, MRI, and endoscopy may be performed based on clinical findings. Management When persistent hiccups adversely affect a patient's quality of life, treatment is absolutely indicated. Given the numerous etiologies of hiccups, treatment should first be directed at rectifying the specific cause as determined by history, physical exam, and testing. The number of therapies directed at the resolution of hiccups far surpasses the numerous etiologies behind the process itself. Anecdotal evidence for nonpharmacologic therapies directed at hiccups abounds. These therapies are aimed at manipulating phrenic and vagal nerve activity and include respiratory maneuvers, nasopharyngeal stimulation, and methods to decrease gastric distention. Such ancient remedies include sneezing, inducing unexpected fright, swallowing granulated sugar, carotid massage, Valsalva maneuvers, supraorbital pressure, holding one's breath, or other various maneuvers to manipulate PaCO2. Targeted pharmacologic therapy is aimed at inhibition of stimulated points in the hiccup reflex arc, largely effecting blockade through inhibitory neurotransmitters. Most pharmacologic therapies have been evaluated in case studies rather than in controlled clinical trials. Idiopathic chronic hiccups have been treated with such pharmacologic agents as GABA and dopamine antagonists (baclofen, chlorpromazine, haloperidol, metoclopramide); anticonvulsants (valproic acid, carbamazepine, phenytoin); and numerous miscellaneous agents (nifedipine, sertraline, anesthetics, gastric acid suppressors). In a small number of case studies, gabapentin has been reported as successful therapy in refractory hiccups. Hiccups usually respond rapidly to therapy if the therapy is to be effective. However, multiple agents may be initiated before a successful drug is found. In cases refractory to both conservative (nonpharmacologic) and pharmacologic therapy, surgical manipulation of either the phrenic or vagal nerves may need to be considered.