Cindy Mui MD
Faculty Peer Reviewed
Hiccups, or singultus, are sudden, involuntary contractions of the diaphragm, which are terminated by abrupt closure of the glottis, producing their characteristic sound. Hiccups serve no known physiologic purpose, and descriptions of their causes and “cures” date back to the time of Hippocrates. The sheer number of remedies for hiccups prompted Dr. Charles Mayo, a physician at the turn of the 20th century and one of the founders of the Mayo clinic, to state “there is no disease which has had more forms of treatment and fewer results from treatment than has persistent hiccup.” Usually benign and even amusing since nearly everyone has had them at some point, it continues to serve as a subject of medical curiosity.It is thought that hiccups occur from stimulation of a hiccup reflex arc. The arc includes an afferent limb comprised of the vagus and phrenic nerves and the sympathetic chain arising from the T6-12 thoracic segments, a central coordination center in the spinal cord between C3 and C5 with connections to the brainstem and hypothalamus. The efferent limb involves the phrenic nerve with connections to the glottis and inspiratory intercostal muscles (1,2). Hiccups can be further defined by duration; hiccup bouts lasting more than 48 hours but less than 1 month are defined as persistent while those lasting more than 1 month are defined as intractable (2). Persistent or intractable hiccups can be distressing and debilitating, causing weight loss due to an inability to eat, exhaustion, insomnia, arrhythmias, wound dehiscence, and even death. Further, hiccup bouts lasting this long may be a sign of an underlying disease (1).
Benign, self-limited hiccups, similar to belching (eructation or burping), are most frequently caused by gastric distension from overeating, drinking carbonated beverages or alcohol, or aerophagia. The proposed mechanism by which distension causes hiccups is due to stretching, activating the gastric branches of the vagus nerve or direct stimulation of the diaphragm, resulting in stimulation of the hiccup arc. Alcohol ingestion also acts to remove normal inhibition of the hiccup arc, explaining the classic description of the hiccupping drunkard. Sudden changes in body or environmental temperature or sudden emotional stress may also lead to transient hiccups by stimulating the hiccup arc (1). Persistent or intractable hiccups can be due to over 100 underlying diseases.
Some causes of persistent and intractable hiccups (1)
Central nervous system: Structural lesions: neoplasms, hydrocephalus
Vascular lesions: arteriovenous malformations, intracranial hemorrhage, vascular insufficiency
Infectious: meningitis, encephalitis, abscess, neurosyphillis
Toxic-metabolic:: Diabetes mellitus, uremia, electrolyte abnormalities, fever
Diaphragmatic irritation: Hiatal hernia, hepatosplenomegaly, esophageal cancer, myocardial infarction, aberrant cardiac pacemaker electrode
Vagus nerve irritation: Mediastinal or thoracic tumors or infections, enlarged lymph nodes, goiter, peptic ulcer, thoracic or abdominal abscess
Psychiatric :Malingering, anorexia nervosa
Pharmacologic: Dexamethasone, barbiturates, diazepam, alpha methyldopa
Treatment for intractable hiccups should be directed at the underlying cause if known with pharmacologic therapy reserved for idiopathic cases when all else has failed. Most of the home remedies are based on case reports or series but some have a physiologic basis. Several remedies involve stimulating the nasopharynx. These remedies, which include forcible traction of the tongue, gargling water, drinking from the far side of the glass, swallowing granulated sugar or ice cubes quickly, may function by disrupting the vagal afferent limb of the hiccup reflex arc. Even when ineffective, these maneuvers are usually quite benign, with the worst adverse event being the potential for spilling water down the front of one’s shirt. Direct vagal stimulation, such as by carotid massage, Valsalva maneuver, ocular pressure, and digital rectal massage may also be effective, though digital rectal massage may be a bit of an atypical way to solve the problem of hiccups. Remedies that involve sympathetic nerve stimulation such as startling someone or ejaculation can disrupt the reflex arc as well and may be more enjoyable for some than the previous maneuvers. Breath holding and breathing into a paper bag has been reported to help with hiccups by producing a mild respiratory acidosis, which can have a direct inhibitory effect on diaphragmatic contractility. Other manual maneuvers include C3 to C5 dermatome stimulation by percussion of the back of the neck or acupuncture (1,2,4).
Evidence for pharmacologic treatments is sparse due to the low incidence of intractable hiccups and thus difficulty in enrolling enough patients for large well-designed trials. Of the pharmacologic treatments available, only chlorpromazine, a phenothiazine antipsychotic that acts as a dopamine antagonist in the hypothalamus, has a FDA indication for the treatment of intractable hiccups. However, it is associated with significant adverse effects such as postural hypotension and drowsiness, that limit its use clinically for such a benign disease (5). Baclofen, a gamma aminobutyric acid (GABA) derivative, has had success in the treatment of hiccups by depressing synaptic transmission to spinal sites. Evidence supporting the use of baclofen is mainly from case reports of 7 to 37 patients but one randomized trial of 4 patients showed a subjective improvement with the drug (6,7). The combination of cisapride, omeprazole, and baclofen (COB) was a popular treatment for intractable hiccups in the1990s but cisapride has since been removed from the US market due to safety concerns and gabapentin has emerged as the newest medication to be used for treatment of hiccups, with early studies showing promise. Gabapentin is an amino acid related to the inhibitory neurotransmitter, GABA, and was first suggested as an adjunct to COB therapy after being tested in a case series of 4 patients (8). Several other small case series, including a case series of 15 patients who were followed over 36 months, have also reported symptomatic improvement with minimal adverse effects (9). Despite these encouraging reports, there is currently not enough evidence to recommend its use for intractable hiccups.
Peer Reviewed by Michael Poles MD, Associate Editor, Clinical Correlations
References:
1. Lewis JH. Hiccups: Causes and Cures. J Clin Gastroenterol 1985; 7(6):539-52.
2. Kolodzik PW, Eilers MA. Hiccups (Singultus): Review and Approach to Management. Ann Emerg Med 1991;20:565-73.
3. Samuels L. Hiccup: A ten year review of anatomy, etiology, and treatment. Can Med Assoc J 1952;67:315-22.
4. Peleg R, Peleg A. Case Report: Sexual intercourse as potential treatment for intractable hiccups. Can Fam Physician 2000;46:1631-2.
5. U.S Food and Drug Administration. http://www.fda.gov/cder/foi/label/2001/11120s86lbl.pdf
6. Guelaud C, Similowski T, Bizec JL, et al. Baclofen therapy for chronic hiccup. Eur Respir J 1995;8:235-7.
7. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a double-blind randomized, controlled, cross-over study. Am J Gastroenterol 1992;87(12):1789-91.
8. Petroianu G, Hein G, Stegmeier-Petroianu A, et al. Gabapentin “add-on therapy” for idiopathic chronic hiccup (ICH). J Clin Gastroenterol 2000;30(3):321-4.
9. Moretti R, Torre P, Antonello RM, et al. Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: a three-year follow up. The Neurologist 2004;10:102-6.