Hiccups

Hiccups are produced by repeated involuntary contractions of a hemi-diaphragm. Just after the muscle begins to contract, the glottis shuts off the trachea producing the noise which gives the condition its name. 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.¹ Hiccups are usually self limiting lasting only a short period of time, but may become intractable in a small number of cases, the longest recorded attack lasting 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.²

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 frequently and those episodes lasting 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 reoccur 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:^2,3

• Respiratory - e.g. bronchial tumour, pneumonia, pleurisy, asthma
• Cardiovascular - e.g. myocardial infarction, pericarditis, thoracic aortic aneurysm
• Gastrointestinal - e.g. gastro-oesophageal reflux disease (GORD), duodenal ulcers, appendicitis, inflammatory bowel disease, cholecystitis, bowel obstruction
• Genitourinary - e.g. renal failure, renal tumour, prostate cancer
• Central nervous system - e.g. CVA, malignancy, infection, trauma, multiple sclerosis
• Psychogenic - shock, fear, excitement, attention seeking behaviour
• Irritation of the diaphragm - e.g. subphrenic abscess, hiatus hernia
• Vagus nerve irritation - e.g. tumours, goitre, pharyngitis, meningitis, glaucoma
• Phrenic nerve irritation
• After surgery - e.g. gastric stasis, direct irritation of the nerve, hyperextension of the neck
• Metabolic - e.g. uraemia , hyponatraemia, hypokalaemia, hypo/hyperglycaemia
• Drug induced - e.g. dexamethasone, benzodiazepines, alcohol, opioids, methyldopa

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. 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:

• Urea and electrolytes
• Serum Calcium
• Full blood count
• Blood glucose
• Liver function tests
• Chest Xray
• ECG

Further investigations may be performed as indicated e.g.

• Fluoroscopy of diaphragmatic movement
• Abdominal ultrasound
• CT/MRI scan
• Endoscopy
• Bronchoscopy
• Colonoscopy

Non-drug⁴

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:. e.g. stimulation of the nasopharynx by drinking from the wrong side of a glass or drinking ice cold water. Vagal stimulation e.g. 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.⁵

Phrenic nerve block using local anaesthesia, electrical stimulation or chemical disruption might be considered if hiccups remain unresponsive to drug treatment and cause significant discomfort or morbidity.

General anaesthesia and transoesophageal diaphragmatic pacing have also been helpful in isolated cases.

Drugs

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.⁶ Baclofen has been used in some patients who were unable to tolerate other agents. In patients with severe intractable hiccups ketamine and intravenous lidocaine (lignocaine) have also been used in a specialist setting. Parenteral midazolam may be appropriate for patients with intractable hiccups secondary to terminal cancer.⁷ An H₂-receptor blocker or proton pump inhibitor may also be helpful.⁸

Surgery⁴

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. Gastroesophageal 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.⁴

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.