Hiccups, sore mouth and bad breath

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3 Hiccups, sore mouth and bad breath

Hiccups

Pathophysiology

Electromyographic studies show the reflex involves a transient burst of intense inspiratory activity, involving excitation of the diaphragm and inspiratory intercostal muscles, with reciprocal inhibition of the expiratory intercostal muscles. The discharge burst lasts for approximately 500 ms, but the duration of the inspiratory air flow is very much shorter than this because inspiration is halted abruptly, in the presence of continued powerful inspiratory muscle contraction, by glottal closure 35 ms after the onset of inspiration. This phenomenon generates the noxious sensation and the characteristic sound of hiccups. Glottal closure persists for 1 second or more until the mechanical effect of the hiccups has subsided. Hiccups are most likely to occur during inspiration, suggesting the rate of change of lung volume may be a co-stimulus for the reflex.

The reflex is mediated by afferent fibres primarily in the phrenic and vagus nerves as well as dorsal sympathetic fibres. These fibres synapse within the dorsolateral region of the medulla. The main efferent limb of the reflex causing spasm of the diaphragm is then mediated by motor fibres of the phrenic nerve but also via fibres in the vagus, cervical and thoracic nerves. Hence, hiccups can result from direct stimulation or irritation of the afferent or efferent vagal or phrenic pathways; from lesions in the medulla or they can be secondary to metabolic disturbances.

A range of gastrointestinal stimuli can cause reflex excitation of visceral afferent vagal fibres. Vagal afferent receptors in the oesophagus can trigger the responsible medullary centres. This is the proposed mechanism for hiccups occurring during swallowed bolus impaction at the site of a benign stricture or ring, or in response to oesophageal distension by retained food and fluid in oesophageal achalasia, or in the context of pill-induced oesophageal ulceration or stricture. Similar vagal afferent stimuli might originate in cases of hiatus hernia or gastro-oesophageal reflux disease, but the evidence implicating reflux as a cause of hiccups remains inconclusive.

Although an association between hiccups and reflux has been well described, whether there is a cause-and-effect relationship remains controversial. The association may be fortuitous; reflux may cause hiccups or hiccups may cause reflux. Hiccups transiently create a pressure gradient that favours reflux of gastric content into the oesophagus. Hiccups acutely reduce intraoesophageal pressure by 20–40 mmHg and simultaneously reduce lower oesophageal sphincter pressure. Patients have been described in whom oesophageal acid infusion provoked hiccups, and in whom the treatment of reflux cured the hiccups. However, other investigators could not induce hiccups by acid infusion. Furthermore, there are numerous studies reporting failure of fundoplication to cure hiccups even in the context of demonstrable acid reflux, which argues against a causal relationship between reflux and hiccups.

Are hiccups associated with oesophageal dysmotility? An achalasia-like picture during the symptomatic phase of intractable hiccups has been reported. This pattern reverted partially to normal with resolution of the hiccups. Achalasia, presumably secondary to oesophageal distension, can present with hiccups usually during consumption of a meal—a symptom that is alleviated following pneumatic dilatation. A range of non-specific oesophageal motor abnormalities can co-exist during the symptomatic phase. Oesophageal peristaltic abnormalities have been reported by some to be present during hiccups. Several manometric studies have demonstrated oesophageal aperistalsis in response to swallows while patients were symptomatic and a return to normal motility thereafter in the absence of hiccups. However, at least one study reported normal oesophageal peristalsis during hiccups. A non-specific oesophageal motor disorder, with some features consistent with spasm, was reported in one case.

Aetiology of hiccups

The relatively common self-limiting bout of hiccups is frequently induced by gastric distension, emotion, alcohol ingestion or sudden change in temperature. However, most frequently the cause of transient hiccups is unknown. The cause of intractable hiccups can be classified into five groups (Box 3.1):

Structural or functional disturbances of the dorsolateral medulla, in the region of the vagal nuclei and the nucleus tractus solitarius, can cause hiccups. Medullary lesions causing hiccups include infarction in the territory of the posterior inferior cerebellar artery, tumour, abscess, syrinx, haemangioma, haematoma, aneurysm and demyelination. Central nervous system infections including viral encephalitis, syphilis and HIV encephalopathy are less common central causes for hiccups. Neurogenic hiccups due to brainstem disease are frequently accompanied by localising neurological signs.

Stimulation of visceral afferent vagal fibres originating in the gastrointestinal tract will cause hiccups. Gastro-oesophageal reflux, achalasia, gastric distension, oesophageal or small bowel obstruction and even pancreatic or biliary disease can provide the stimulus in these cases. Vagal afferent stimulation of the auricular branch of the vagus nerve supplying the external auditory canal has reportedly caused hiccups—in one instance the stimulus arose from an insect trapped in the auditory canal. Mediastinal disease (e.g. tumour, thoracic aortic aneurysm or diaphragmatic irritation caused by subphrenic and hepatic disease, pleural or pericardial effusion, or myocardial infarction) can similarly result in hiccups by stimulation of vagal or phrenic nerve fibres within the mediastinum or by direct irritation of the diaphragm.

Systemic and metabolic disorders including diabetes mellitus, chronic kidney disease, hypocalcaemia, hyponatraemia and Addison’s disease can cause hiccups. Drugs, most commonly alcohol and general anaesthetic agents, can cause hiccups but others include corticosteroids, benzodiazepines, barbiturates and etoposide. Psychogenic hiccups have been described, although this is speculative as the reflex is truly involuntary.

Approach to the patient with intractable hiccups

A careful history should enquire about neurological symptoms, particularly headache and brainstem symptoms such as diplopia, vertigo, nausea, vomiting, hoarseness, ataxia or clumsiness, and disordered pain sensation. Chest pain, fever and cough are clues to cardiac, respiratory or mediastinal disease. Gastrointestinal causes may be suspected if heartburn, regurgitation, chest pain, dysphagia, vomiting or abdominal pain is reported. A history of metabolic disorders and drug enquiry are also important (Box 3.2).

Physical examination should include examination of cranial nerve, long tract and cerebellar signs. Disordered cognitive function may relate to metabolic derangements or to central causes such as encephalitis. Cardiorespiratory examination should look for signs of pleural or pericardial disease and postural hypotension, which is present in Addison’s disease. The external auditory canals should be examined for foreign bodies. Abdominal examination should specifically look for signs of gastric stasis (e.g. succussion splash), bowel obstruction or tender hepatomegaly, which may indicate hepatic enlargement, or an intrahepatic lesion such as an abscess.

The priorities with respect to investigations will be dictated by the historical and physical findings. Serum electrolytes including sodium, calcium, blood sugar level and liver function tests should be done. A leucocytosis may indicate an underlying infective process. Chest x-ray and electrocardiogram are important to detect pericardial, plural or myocardial disease such as myocardial infarction. A thoracic computed tomography (CT) scan can be performed if mediastinal disease is suspected. Imaging of the abdomen is indicated if a subdiaphragmatic abscess is suspected. Endoscopy is indicated if oesophageal disease or gastric stasis is apparent clinically. The approach to intractable hiccups is outlined in Box 3.2.