Hiccups

Hiccups are involuntary, repetitive spasmodic contraction of the diaphragm and inspiratory intercostal muscles, followed by abrupt glottic closure about 35 ms later, producing the characteristic sound.

• Reflex arc: afferent via the vagus, phrenic nerve and thoracic sympathetic chain; central coordination in the brainstem and upper cervical cord (hiccup centre near the medulla); efferent via the phrenic nerve to the diaphragm and the recurrent laryngeal nerve to the glottis.
• Duration classes: an attack lasting under 48 hours is acute (benign, self-limiting). Persistent hiccups last more than 48 hours up to 1 month. Intractable hiccups last more than 1 month.
• Acute episodes are usually triggered by gastric distension (large meal, carbonated drinks, rapid eating), alcohol, sudden temperature change in the stomach, emotional excitement or stress.
• Persistent and intractable hiccups are rarely benign. Causes cluster into central (stroke, especially lateral medullary infarct, multiple sclerosis, tumour, encephalitis, meningitis, trauma), peripheral (irritation of the vagus or phrenic nerve by goitre, mediastinal mass, lymphadenopathy, aortic aneurysm, pericarditis, oesophageal disease, hepatic or subphrenic abscess, diaphragmatic irritation), metabolic (uraemia, hyponatraemia, hypokalaemia, hypocalcaemia, hyperglycaemia or diabetic ketoacidosis) and drug related.
• Drugs implicated: dexamethasone and other corticosteroids, benzodiazepines (midazolam, diazepam), opioids, methyldopa, barbiturates, chemotherapy agents (cisplatin, etoposide), ondansetron, anaesthetic agents.
• Male predominance is marked in persistent hiccups (about 80 percent).
• Prognosis: acute hiccups resolve spontaneously. Persistent hiccups can cause insomnia, exhaustion, weight loss, dehydration, aspiration, wound dehiscence and depression.

• Sudden audible "hic" at 4 to 60 episodes per minute, usually regular in rate within an individual.
• Usually stops during sleep in functional or gastric causes. Hiccups persisting through sleep point towards a structural central cause.
• Symptoms of the trigger: epigastric fullness, belching, reflux.
• Red flags: hiccups lasting more than 48 hours, associated dysphagia, weight loss, haemoptysis, neck mass, focal neurological signs, vertigo, ataxia, diplopia or facial numbness (brainstem lesion), chest pain, fever, cough, sweating, alcohol dependence, known malignancy, recent chemotherapy or surgery, new drug (especially corticosteroid).
• Examination: ENT examination of the external ear canal (irritation of the auricular branch of the vagus by hair or foreign body can trigger hiccups), neck (goitre, nodes), chest (effusion, consolidation), abdomen (hepatomegaly, mass, distension), full cranial nerve and cerebellar examination, fundoscopy, blood pressure.

• Acute hiccups with no red flags: clinical diagnosis, no investigations.
• Persistent or intractable hiccups (more than 48 hours):
  • Bloods: full blood count, urea, creatinine, electrolytes (sodium, potassium, calcium, magnesium), glucose, liver function tests, amylase, CRP, thyroid function.
  • Chest X-ray (mediastinal mass, pneumonia, effusion, raised hemidiaphragm).
  • ECG and, if chest pain, troponin (inferior myocardial infarction, pericarditis).
  • Upper gastrointestinal endoscopy if reflux symptoms, dysphagia or epigastric pain.
  • Neck and abdominal ultrasound if clinical suspicion.
  • Consider CT of chest, abdomen and pelvis, and MRI brain and cervical spine with brainstem protocol if neurological features or unexplained after the initial tests.
• Drug history review: stop or switch the likely offending drug where possible.

• Acute hiccups:
  • Reassurance. Physical manoeuvres: breath holding for 10 to 20 seconds, Valsalva manoeuvre, sipping iced water, swallowing a teaspoon of granulated sugar, gentle traction on the tongue, drinking from the far side of a glass, pulling the knees to the chest and leaning forward to compress the diaphragm, rebreathing into a paper bag (avoid in cardiorespiratory disease).
  • Avoid large meals, carbonated drinks and alcohol while symptomatic.
• Persistent or intractable hiccups: treat the cause first (stop the offending drug, correct electrolytes, treat reflux, drain abscess, treat tumour). Start symptomatic drugs in parallel:
  • First line: omeprazole 20 mg orally once daily (40 mg in severe reflux) for 4 weeks if gastro oesophageal reflux is a plausible driver.
  • Metoclopramide 10 mg orally or intravenously three times daily for up to 5 days (maximum 30 mg per day; reduce to 5 mg three times daily in renal impairment with creatinine clearance under 40 mL/min, and in those under 60 kg). Avoid in Parkinson disease, epilepsy, phaeochromocytoma and intestinal obstruction. Risk of acute dystonia and tardive dyskinesia with prolonged use.
  • Baclofen 5 mg orally three times daily, increased by 5 mg per dose every 3 days to a maximum of 20 mg three times daily (60 mg per day); in the elderly and renal impairment start at 5 mg once or twice daily and titrate slowly. Do not stop abruptly (withdrawal seizures, hallucinations). Caution in epilepsy, stroke and psychiatric illness.
  • Gabapentin 300 mg orally at night, increased by 300 mg every 3 days to 300 to 600 mg three times daily (maximum 3600 mg per day); reduce in renal impairment (creatinine clearance 30 to 59 mL/min: 400 to 1400 mg per day in two divided doses; 15 to 29: 200 to 700 mg once daily).
  • Chlorpromazine 25 to 50 mg orally three to four times daily for up to 10 days; or 25 to 50 mg intramuscularly once, then 25 to 50 mg intravenously diluted in 500 to 1000 mL of normal saline over 1 hour (monitor blood pressure, postural hypotension, QTc, sedation). Avoid in the elderly with dementia, Parkinson disease, QTc prolongation.
  • Haloperidol 1 to 2 mg orally three times daily (0.5 mg in the frail elderly); check QTc before and after starting.
  • Amitriptyline 10 to 25 mg orally at night, increased gradually to 50 to 75 mg (alternative in neuropathic or central cases).
  • Nifedipine 10 mg orally three times daily (limited evidence; monitor blood pressure).
  • Sodium valproate 15 mg/kg/day orally in two or three divided doses, titrated to 40 mg/kg/day, in refractory cases (avoid in women of childbearing potential without contraception; monitor liver function and full blood count).
• Refractory: refer for phrenic nerve block or stimulation, and for specialist assessment.
• In palliative care and cancer related hiccups, dexamethasone induced hiccups often respond to a dose reduction; use metoclopramide or baclofen first.
• Safety: aspiration risk in the sedated or those with neurological disease; keep upright when eating; monitor hydration and weight.
• Referral: urgent assessment for red flag features, suspected brainstem lesion, hiccups more than 1 month, and failure of two drug courses.