Approach
The diagnosis of hiccups is clinical and derived primarily from a thorough clinical history. The underlying cause of chronic hiccups is identified through a focused history, physical examination, and targeted investigations. Depending on the initial findings, referral to an appropriate specialist may be required to direct further investigations and initiate treatment of any underlying condition.
Clinical history
The severity, duration, predisposing factors, and characteristics of the hiccups, as well as a description of previous episodes, should be established. Hiccups are characterised by a distinctive 'hic' sound resulting from sudden glottic closure interrupting an abrupt inhalation secondary to diaphragmatic spasm. The duration and intensity of hiccups allows differentiation between benign self-limiting hiccups and chronic hiccups; those lasting >48 hours and often associated with other symptoms and complications are classified as chronic. Chronic hiccups during sleep suggests an organic cause and may lead to insomnia, with subsequent fatigue and exhaustion during the day.[15] This in turn leads to impaired alertness and concentration, with consequences for work and social activities.
Predisposing factors include excessive food or alcohol consumption, drinking carbonated beverages, sudden changes in ambient or gastrointestinal temperature (e.g., cold showers, drinking hot or cold beverages), sudden excitement, and emotional stress.[5]
A thorough past medical and drug history, as well as a systems review, should follow. It is important to obtain information regarding conditions that can affect the hiccup reflex arc.
Diaphragmatic and phrenic nerve irritation may result from subphrenic abscess, splenomegaly, hepatomegaly, myocardial infarction, pericarditis, a hiatus hernia, oesophageal cancer, or an aberrant cardiac pacemaker electrode.
Irritation of the vagus nerve may result from a foreign body irritating the tympanic membrane, pharyngitis, laryngitis, a goitre or neck cyst, pneumonia, empyema, bronchitis, asthma, pleuritis, tuberculosis, lung cancer, oesophagitis, aortic aneurysm, cor pulmonale, mediastinitis, gastric atony, gastric cancer, gastritis, duodenal ulcer, pancreatitis, pancreatic cancer, intra-abdominal abscess, bowel obstruction, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's disease, gastrointestinal haemorrhage, appendicitis, hepatitis, or prostatic disease.[6][7][8][9]
Central nervous system causes include structural lesions (intracranial neoplasm, syringomyelia, multiple sclerosis, ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or infarction, arterio-venous malformation, vascular insufficiency), infection (meningitis, encephalitis, neurosyphilis, malaria, herpes zoster), trauma, and epilepsy.[10][11][12]
Metabolic causes include uraemia, diabetes mellitus, gout, hyponatraemia, hypocalcaemia, hypokalaemia, and alkalosis. Electrolyte disturbances can decrease the central inhibition of the hiccup reflex arc, leading to chronic hiccups.
Cancer chemotherapy can cause predictable, episodic hiccups that can be troubling to patients with cancer.[14]
Dyspnoea, cough, sputum, and pleuritic chest pain indicate possible pulmonary involvement. Gastrointestinal involvement is indicated by such symptoms as abdominal pain, heartburn, vomiting, diarrhoea, jaundice, dysphagia, and odynophagia. Seizures and peripheral sensory and motor symptoms are indicative of possible central nervous system involvement. Fever, unexplained weight loss, and night sweats may indicate an underlying malignancy such as oesophageal, lung, gastric, or pancreatic cancer.
The presence of chronic diseases such as diabetes mellitus, gout, and renal insufficiency should be noted, and a detailed drug history should pay particular attention to dexamethasone, diazepam, sulfonamides, anti-epileptics, and alpha-methyldopa. History of smoking, alcohol consumption, and illicit drug use should be established. Psychological involvement is suggested by a history of personality disorder, conversion reaction, hysterical neurosis, anorexia nervosa, sudden shock, and grief reaction.[8][17]
Physical examination
The physical examination in benign hiccups is unremarkable; however, it may reveal signs of the underlying cause of chronic hiccups.
There may be evidence of weight loss and malnutrition secondary to chronic hiccups. Assessment of the neck region may show evidence of trauma, or reveal a foreign body in the auditory canal, nuchal rigidity, a goitre or neck cyst, cervical lymphadenopathy, or pharyngitis. Examination of the respiratory system may reveal conditions such as asthma, pneumonia, empyema, tuberculosis, or pleuritis. Abdominal examination may reveal splenomegaly, hepatomegaly, an abdominal aortic aneurysm, or an acute abdomen (e.g., cholecystitis, cholelithiasis, pancreatitis, appendicitis, intestinal obstruction, rupture of a hollow viscus). Neurological examination may show evidence of a stroke, meningismus, encephalitis, or a space-occupying lesion.[15]
Laboratory investigations
A routine blood panel including full blood count, urea, and serum electrolytes should be undertaken in all patients with chronic hiccups. The selection of other laboratory tests such as liver function tests, gamma glutamyl transpeptidase, C-reactive protein and erythrocyte sedimentation rate, serum amylase, an arterial blood gas, and a toxicology screen (including blood alcohol) is dictated by the results of the clinical history and physical examination.[1]
Investigation of the underlying cause
Further investigations to identify the underlying cause of chronic hiccups are directed by the clinical history, physical examination findings, and initial investigation results, and may include assessment of conditions related to the cardiac, respiratory, gastrointestinal, and neurological systems.
A chest x-ray, pulmonary function tests, and ECG may be undertaken to identify pulmonary, mediastinal, and cardiac aetiologies (e.g., myocardial infarction, pericarditis, an aberrant cardiac pacemaker electrode, pneumonia, empyema, bronchitis, asthma, pleuritis, aortic aneurysm, tuberculosis, lung cancer, cor pulmonale, and mediastinitis) capable of irritating the phrenic and vagus nerves, or the diaphragm itself.[16]
Computed tomography (CT) or magnetic resonance imaging of the head and a lumbar puncture may reveal neurological aetiologies, including structural lesions (intracranial neoplasm, syringomyelia, multiple sclerosis, ventriculo-peritoneal shunt), vascular lesions (intracranial haemorrhage or infarction, arterio-venous malformation, vascular insufficiency), infection (meningitis, encephalitis, neurosyphilis, malaria, herpes zoster), and trauma.[10][11][12]
Endoscopy of the upper gastrointestinal tract and an abdominal CT may be undertaken to identify gastrointestinal aetiologies such as oesophagitis, oesophageal cancer, duodenal ulcer, gastritis, subphrenic abscess, splenomegaly, hepatomegaly, hiatus hernia, gastric cancer, pancreatitis, pancreatic cancer, intra-abdominal abscess, bowel obstruction, abdominal aortic aneurysm, cholecystitis, cholelithiasis, ulcerative colitis, Crohn's disease, gastrointestinal haemorrhage, appendicitis, and hepatitis.
Otoscopy and pharyngoscopy may reveal a foreign body irritating the tympanic membrane, or pharyngitis, respectively.
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