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Synonyms: hiccoughs, singultus (from the Latin singult = 'the act of catching one's breath while sobbing')
Hiccups are produced by repeated involuntary contractions of a hemidiaphragm. Just after the muscle begins to contract, the glottis shuts off the trachea producing the noise which gives the condition its name. Often only one hemidiaphragm is affected; in 80% of cases this is on the left side. Hiccups appear to serve no useful purpose in humans but have been observed in fetuses in utero. It has been postulated that they represent a primitive reflex similar to that of the opening and closing of gills in some lower vertebrate animals. Hiccups are usually self-limiting, lasting for only a short period of time but may become intractable in a small number of cases, the longest recorded attack lasting for 60 years. The neural control of the hiccup reflex is thought to involve the phrenic and vagus nerves together with the sympathetic chain from T6-T12, the respiratory centre, medullary reticular formation and the hypothalamus.
Hiccups are extremely common and are experienced by most people at some time in their life. Women and men appear to be equally affected, although prolonged and intractable hiccups are more common in men. Hiccups may occur at any age. Hiccups occur mainly in the evening. They are more common in the first half of the menstrual cycle, especially in the few days before menstruation. They are much reduced in pregnancy.
Causes of hiccups
Hiccups occur frequently and those episodes lasting for only short periods of time may have no apparent underlying cause, or may occur after eating a large meal, drinking alcohol during periods of excitement or due to sudden changes in air temperature. Hiccups which recur very frequently, or last for more than 48 hours, may be an indication of an underlying physical problem. Many causes of hiccups have been described; however, often no cause is found. Some of the more common underlying causes of prolonged bouts of hiccups include:
- Respiratory - eg bronchial tumour, pneumonia, pleurisy, asthma.
- Cardiovascular - eg myocardial infarction, pericarditis, thoracic aortic aneurysm, arrhythmia-induced syncope, chronic myocardial ischaemia.
- Gastrointestinal - eg gastro-oesophageal reflux disease (GORD), duodenal ulcers, appendicitis, inflammatory bowel disease, cholecystitis, bowel obstruction.
- Genitourinary - eg renal failure, renal tumour, prostate cancer.
- Central nervous system - eg cerebrovascular accident, malignancy, infection, trauma, multiple sclerosis, brainstem lesions, lateral medullary ischaemia.
- Psychogenic - shock, fear, excitement, attention seeking behaviour.
- Irritation of the diaphragm - eg subphrenic abscess, hiatus hernia.
- Vagus nerve irritation - eg tumours, goitre, pharyngitis, meningitis, glaucoma.
- Phrenic nerve irritation.
- After surgery - eg gastric stasis, direct irritation of the nerve, hyperextension of the neck.
- Metabolic - eg uraemia, hyponatraemia, hypokalaemia, hypoglycaemia, /hyperglycaemia.
- Drug-induced - eg dexamethasone, benzodiazepines, alcohol, opioids, methyldopa.
- Sarcoidosis - hiccups associated with mediastinal lymph nodes have been reported.
As the underlying causes of hiccups are many and varied, it is not practical to arrange an exhaustive battery of investigations to determine what, if any, is the nature of the precipitating pathology. A detailed history and examination are of paramount importance when deciding which investigations should be performed. An organic cause can be found in 93% of men and 8% of women. If the history and examination yield no apparent area which should receive particular attention it is not unreasonable to perform simple screening investigations such as:
- Serum calcium
- Blood glucose
Further investigations may be performed as indicated - for example:
- Fluoroscopy of diaphragmatic movement
- Abdominal ultrasound
- CT/MRI scan
Most bouts of hiccups will be self-limiting and will require no treatment. Several remedies are common in folklore and many have a physiological basis to explain their apparent success: eg stimulation of the nasopharynx by drinking from the wrong side of a glass or drinking ice-cold water. Vagal stimulation, eg by means of the Valsalva manoeuvre, breath holding or breathing into a paper bag, may also work.
- Stimulation of the nasopharynx: by sipping iced water, swallowing granulated sugar, tasting vinegar or biting on a lemon.
- Interruption of normal respiratory function: Valsalva manoeuvre, breath holding, hyperventilation or breathing into a paper bag, inducing sneezing.
- Counter-irritation of the diaphragm: leaning forward to compress the chest or pulling the knees up to the chest.
There is some evidence that acupuncture and hypnotherapy are beneficial.
Interruption of the phrenic nerve by local anaesthetic block, electrical stimulation or chemical disruption may be indicated in cases unresponsive to drug treatment.
Phrenic nerve block and ultrasound-guided pulsed radiofrequency lesioning (disruption of neuron function using radiofrequency stimulation) have both been found to be helpful in refractory cases.
General anaesthesia and transoesophageal diaphragmatic pacing have also been helpful in isolated cases. Accidental cure after cardioversion has been reported.
Several drugs have been used with good effect in the treatment of prolonged bouts of hiccups. Chlorpromazine is the most commonly used and is effective in 75-80% of cases. Haloperidol has also been used with some success. Working on the basis that prolonged hiccups represent clonic activity of the diaphragm, anticonvulsant drugs have also been used in normal therapeutic doses. Metoclopramide may be successful, particularly if the hiccups are due to gastric stasis or distension. Phenytoin, sodium valproate, carbamazepine and, more recently, gabapentin have all been used with good effect (but note there is one report of hiccups caused by an adverse reaction to phenytoin). Baclofen has been used in some patients who were unable to tolerate other agents.
Amitriptyline, nifedipine and dexamethasone have all been reported to have been beneficial.
In patients with severe intractable hiccups, ketamine and intravenous lidocaine have also been used in a specialist setting. Parenteral midazolam may be appropriate for patients with intractable hiccups secondary to terminal cancer. One study also reported the successful use of baclofen in cancer patients.
Microvascular decompression of the vagus nerve is very occasionally performed when all other therapies have failed.
Surgical interruption of the phrenic nerve has also been used for intractable cases but the surgery itself carries a significant mortality and is a procedure of last resort.
The major complications of prolonged hiccups are psychological, caused by the disruption to normal life and exacerbated by sleep disturbance. Gastro-oesophageal reflux and cardiac arrhythmias have also been noted to develop as a consequence of prolonged hiccups. Severe cases can lead to exhaustion, malnutrition, weight loss, dehydration, wound dehiscence and aspiration pneumonia.
The prognosis for prolonged hiccups for which no obvious cause is found is good, most cases resolving with treatment or remitting spontaneously. The prognosis for patients in which there is an underlying pathology producing the hiccups will depend on the prognosis for that pathology.
Further reading & references
- Marinella MA; Diagnosis and management of hiccups in the patient with advanced cancer. J Support Oncol. 2009 Jul-Aug;7(4):122-7, 130.
- Wilkes G; Hiccups, Medscape, Jul 2010
- Straus C, Vasilakos K, Wilson RJ, et al; A phylogenetic hypothesis for the origin of hiccough. Bioessays. 2003 Feb;25(2):182-8.
- Buyukhatipoglu H, Sezen Y, Yildiz A, et al; Hiccups as a sign of chronic myocardial ischemia. South Med J. 2010 Nov;103(11):1184-5.
- Arami MA; A case of brainstem cavernous angioma presenting with persistent hiccups. Acta Med Iran. 2010 Jul-Aug;48(4):277-8.
- Mandala M, Rufa A, Cerase A, et al; Lateral medullary ischemia presenting with persistent hiccups and vertigo. Int J Neurosci. 2010 Mar;120(3):226-30.
- Lin LF, Huang PT; An uncommon cause of hiccups: sarcoidosis presenting solely as hiccups. J Chin Med Assoc. 2010 Dec;73(12):647-50.
- Calvo E, Fernandez-La Torre F, Brugarolas A.; Cervical phrenic nerve block for intractable hiccups in cancer patients. J Natl Cancer Inst. 2002 Aug 7;94(15):1175-6.
- Renes SH, van Geffen GJ, Rettig HC, et al; Ultrasound-guided continuous phrenic nerve block for persistent hiccups. Reg Anesth Pain Med. 2010 Sep-Oct;35(5):455-7.
- Kang KN, Park IK, Suh JH, et al; Ultrasound-guided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Korean J Pain. 2010 Sep;23(3):198-201. Epub 2010 Aug 26.
- Asadi-Pooya AA, Petramfar P, Taghipour M; Refractory hiccups due to phenytoin therapy. Neurol India. 2011 Jan-Feb;59(1):68.
- Jatoi A; Palliating hiccups in cancer patients: moving beyond recommendations from Leonard the lion. J Support Oncol. 2009 Jul-Aug;7(4):129-30
- Seker MM, Aksoy S, Ozdemir NY, et al; Successful treatment of chronic hiccup with baclofen in cancer patients. Med Oncol. 2011 Mar 26.
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Dr Laurence Knott
Dr Laurence Knott
Prof Cathy Jackson