• If hiccups have lasted more than 48 hours, perform a full assessment to assess whether there is an underlying cause.
• Exclude a possible underlying cause based on history and clinical findings. This usually requires referral to secondary care, but baseline investigations that may be considered in primary care include:
• Full blood count (anaemia may indicate gastrointestinal pathology).
• Erythrocyte sedimentation rate or C-reactive protein level (an elevated level suggests the presence of an underlying disease).
• Urea and electrolytes, creatinine (to exclude uraemia, hyponatraemia, hypokalaemia).
• Blood glucose (to exclude hyperglycaemia).
• Liver function tests (abnormal results may indicate hepatitis, liver metastases).
• Serum calcium (to exclude hyper- or hypocalcaemia).
• Electrocardiogram (to exclude pericarditis, recent myocardial infarction).
• Chest radiograph (to exclude lung pathology).

• Many causes of hiccups have been reported, including:
• Abdominal: gastric distension, gastric reflux, gastritis, small bowel obstruction, cholecystitis, subphrenic abscess.
• Head and neck: tumour, cyst, goitre, pharyngitis, irritation of tympanic membrane (e.g. by a foreign body).
• Thorax: tumours, pneumonia, pericarditis, myocardial infarction, aortic aneurysm.
• Central nervous system: trauma, infection (e.g. cerebral abscess, encephalitis), stroke, tumours, multiple sclerosis.
• Metabolic: uraemia, hypokalaemia, hypocalcaemia, hyperventilation, uncontrolled diabetes mellitus, alcohol, Addison's disease.
• Surgical: anaesthesia, neck extension, post-operative (intra-abdominal, thoracotomy, craniotomy).
• Psychogenic: stress, excitement, reaction to bereavement (grief), anorexia nervosa, malingering.
• Drugs: corticosteroids, benzodiazepines, barbiturates, opioids, methyldopa.

[Lewis, 1985; Howard, 1992; Launois et al, 1993; Rousseau, 1995; Cymet, 2002; Smith and Busracamwongs, 2003]

• CKS recommends a full assessment of a person with prolonged hiccups, because this often indicates an underlying cause [Launois et al, 1993; Schuchmann and Browne, 2007]. In a retrospective study, hiccups lasting more than 48 hours were more likely to be associated with an organic or anatomic cause [Cymet, 2002].
• A study of causative factors in people with intractable hiccups (study duration almost 30 years) found that 93% of 181 males had organic disease and 92% of 36 females had psychogenic hiccups [Souadjian and Cain, 1968].
• The suggestion of which investigations to consider is based on discussion in review articles [Kolodzik and Eilers, 1991; Rousseau, 1995].