Hiccups

A hiccup is a quick, involuntary contraction of the diaphragm that triggers inspiration and audible, reflexive vocal-cord closure. Hiccups are typically caused by irritation along the hiccup reflex arc, which includes the vagus, phrenic, and sympathetic nerves, the hiccup center in the midbrain, and motor nerves innervating the diaphragm and intercostal muscles. Hiccups may be transient (≤ 48 hours), persistent (> 48 hours), or intractable (> 1 month). Etiologies include gastrointestinal disorders (especially gastroesophageal reflux disease), metabolic abnormalities, medications, CNS disease, thoracic pathology, and psychogenic or idiopathic causes. Evaluation of persistent or intractable hiccups involves a focused history, targeted examination, and initial studies (e.g., CBC, CMP, chest x-ray, and ECG). Further assessment with imaging or endoscopy is guided by the presence of red flags for hiccups. Management involves treating the underlying cause and using physical maneuvers and empiric PPIs if no cause is identified. If symptoms persist, medications such as baclofen, gabapentin, or metoclopramide may be used. Invasive interventions can be considered for refractory hiccups.

• Transient hiccups: duration ≤ 48 hours
• Persistent hiccups: duration > 48 hours
• Intractable hiccups: duration > 1 month

Persistent and intractable hiccups require evaluation for an underlying cause. ^[1]

Hiccups are typically caused by irritation or injury to the hiccup reflex arc.

Gastrointestinal and abdominal causes ^[1]

• Esophageal causes
  • Gastroesophageal reflux disease (GERD)
  • Esophagitis
  • Esophageal cancer
• Gastric causes
  • Hiatal hernia ^[2]
  • Gastritis (e.g., Helicobacter pylori infection)
  • Peptic ulcer disease
  • Gastric distension
  • Gastric outlet obstruction
  • Gastric cancer
• Other
  • Bowel obstruction
  • Pancreatitis
  • Gallbladder disease
  • Hepatitis ^[3]
  • Ascites
  • Abdominal abscess
  • Abdominal tumor (e.g., colon cancer, pancreatic cancer)

GERD is the most common cause of persistent hiccups. ^[3]

Metabolic causes ^[1]

• Hyponatremia
• Hypokalemia
• Hypocalcemia
• Uremia
• Hyperglycemia
• Hypocapnia ^[2]

Medications ^[1]

• Glucocorticoids
• Diazepam
• Opioids
• Antibiotics (e.g., macrolides) ^[2]
• Chemotherapy (e.g., cisplatin, cyclophosphamide, docetaxel)
• Dopamine agonists ^[2]

Central nervous system causes ^[1]

• Vascular
  • Ischemic stroke
  • Hemorrhagic stroke
  • Intracranial hemorrhage
• Infectious
  • Encephalitis
  • Meningitis
  • Brain abscess
  • Toxoplasmosis
• Other ^[2]
  • Head trauma
  • CNS tumor
  • Parkinson disease
  • Multiple sclerosis

Thoracic causes ^[1]

• Myocardial infarction
• Pericardial effusion
• Pericarditis
• Pneumonia
• Empyema
• Pleurisy
• Tumor

Otolaryngeal causes ^[2]

• Otitis media
• Foreign body in the ear
• Foreign body in the nose
• Rhinitis
• Pharyngitis

Perioperative causes ^[2]

• Anesthesia
• Intubation
• Thoracic or abdominal surgery
• Endoscopy
• Central venous catheter placement

Other causes ^[2]

• Psychogenic (e.g., fear, anxiety, stress)
• Idiopathic

Serious and/or life-threatening causes of hiccups include central nervous system causes (e.g., stroke, meningitis, brain tumor), cardiac causes (e.g., myocardial infarction, pericardial effusion), and some abdominal causes (e.g., bowel obstruction, pancreatitis, abdominal tumor). ^[1]

Focused history ^[1]

• Duration: ≤ 48 hours or > 48 hours
• Timing: Nocturnal hiccups often indicate an organic cause.
• Severity: including presence and severity of associated symptoms
  • Vomiting
  • Dehydration, inadequate nutritional intake
  • Fatigue, disrupted sleep
  • Depressed mood, anxiety
• Symptoms of an underlying condition
  • Gastrointestinal (e.g., dyspepsia, abdominal pain)
  • Cardiopulmonary (e.g., chest pain, dyspnea, cough)
  • Neurological (e.g., headache, visual changes, ataxia)
  • Systemic (e.g., fever, malaise)
• Background
  • Past medical history
  • Detailed medication list (e.g., chemotherapy, benzodiazepines)
  • History of invasive procedures (e.g., surgery, endoscopy)
  • Social history: alcohol intake, smoking history, recreational substance use ^[3]

Alcohol use and smoking increase the risk of gastrointestinal and pulmonary causes of hiccups. ^[2]

Focused examination ^[1]

Examination is guided by the history and may include the following:

• Abdominal examination
• Neurological examination: including cranial nerve examination
• Cardiovascular examination
• Pulmonary examination
• Head and neck examination: including otoscopy (e.g., for ear foreign body, infection, impacted cerumen) ^[3]

Red flags for hiccups ^[1][3]

• Nocturnal hiccups
• Recurrent hiccups that occur at regular intervals (may signify an intracranial lesion)
• Clinical features of a serious underlying condition (e.g., chest pain, headache, focal neurological deficit)

Initial studies ^[1][3]

Perform the following studies for all patients with persistent hiccups. Findings vary based on the underlying etiology of hiccups.

• Laboratory studies
  • CBC
  • BMP
  • Liver chemistries
  • POC glucose
• Chest x-ray: to evaluate for thoracic causes
• ECG: to evaluate for ECG findings in ACS

Persistent hiccups require an evaluation for an underlying cause.

Refer patients for urgent evaluation if they have red flag features of hiccups and/or significant diagnostic findings (e.g., ECG findings in ACS). ^[3]

Further studies ^[1][3]

Further studies and the evaluation setting should be guided by the clinical picture. ^[1]

• Diagnostics for GERD: in patients with symptoms of GERD or if hiccups are the only symptom ^[3]
• Imaging: to identify etiologies involving the hiccup reflex arc ^[2]
  • CT chest
  • CT abdomen
  • CT head
  • MRI head and neck
• Other procedures: based on suspected etiology, e.g.,
  • Lumbar puncture: to assess for CNS malignancy and infection
  • Bronchoscopy: in patients with pulmonary symptoms
  • Transthoracic echocardiogram or focused cardiac ultrasound: in patients with clinical features of pericardial effusion

Approach ^[3]

• Treat the underlying cause if identified.
• Counsel patients to avoid gastric irritation (e.g., carbonated drinks, excessive alcohol, rapid eating).
• Attempt a trial of physical maneuvers (e.g., holding breath, uninterrupted drinking, Valsalva maneuver).
• Consider pharmacotherapy.
• Consider referral for an invasive procedure (e.g., phrenic nerve block, vagus nerve stimulation) if pharmacotherapy is unsuccessful.

Pharmacotherapy ^[3]

• First-line: empiric PPI (e.g., omeprazole ) and antacid (e.g., aluminum hydroxide/magnesium carbonate ) ^[2]
• Second-line: if the underlying cause is not identified or treatment of the underlying cause is not possible ^[2]
  • CNS causes: baclofen (off-label) , gabapentin (off-label) ^[2]
  • Other causes: metoclopramide (off-label) ^[2]
  • Alternative (for CNS and/or other causes): chlorpromazine ^[2]