- Author: Garry Wilkes, MBBS, FACEM; Chief Editor: Steven C Dronen, MD, FAAEM more...
Brief episodes of hiccups are a common part of life; however, prolonged attacks are a more serious phenomenon and have been associated with significant morbidity and even death.
Signs and symptoms
No medical training is required to recognize hiccups. However, persistent and intractable hiccups frequently are associated with an underlying pathologic process, and efforts must be made to identify causes and effects. The history should address the following:
- Surgical history
- Comprehensive drug history
- Indicators of psychogenic origin
- Arrhythmia-induced syncope
- Gastroesophageal reflux
- Weight loss
- Emotional distress
- Alcoholism and acute alcohol ingestion
A complete and focused physical examination may yield evidence of the following:
- Head – Foreign body or aberrant hair adjacent to tympanic membrane; glaucoma
- Mouth - Pharyngitis
- Neck – Inflammation; mass lesions; goiter; voice abnormalities; stiffness
- Chest – Tumors; pneumonia; asthma
- Cardiovascular system – Arrhythmias; myocardial infarction (MI); pericarditis; unequal pulses
- Abdomen – Gastric atony; organomegaly; subphrenic abscess; cholecystitis; appendicitis; abdominal aortic aneurysm (AAA); pancreatitis; peritonitis
- Rectum – Mass lesions
- Nervous system – Focal lesions; disordered higher mental function; indications of multiple sclerosis
See Presentation for more detail.
Laboratory testing is directed toward suspected abnormalities as follows:
- Electrolytes - Hyponatremia, hypokalemia, hypocalcemia, and hyperglycemia
- Renal function tests - Uremia
- Liver function tests - Hepatitis
- Amylase and lipase levels - Pancreatitis
- White blood cell (WBC) count
- Urine, sputum, or cerebrospinal fluid (CSF) - Infection
Imaging modalities that may be helpful in the workup include the following:
- Chest radiography
- Fluoroscopy of diaphragmatic movement
- Computed tomography (CT) of the head, thorax, and abdomen
- Magnetic resonance imaging (MRI)
Other studies that may be helpful include the following:
- Nerve conduction studies
- Endoscopy or bronchoscopy
- Esophageal acid perfusion test
See Workup for more detail.
A definitive cure for hiccups has not yet been established. Treatment, if needed, may be pharmacologic or nonpharmacologic.
Pharmacologic therapies include the following:
- Chlorpromazine (drug of choice)
- Valproic acid
Other agents reported to be beneficial are as follows:
- Muscle relaxants (not benzodiazepines, see Etiology)
- Analgesics (eg, orphenadrine, amitriptyline, chloral hydrate, and morphine)
- Stimulants (eg, ephedrine, methylphenidate, amphetamine, and nikethamide)
- Miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, and nifedipine)
Nonpharmacologic therapies include the following:
- Techniques affecting components of the hiccup reflex - Stimulation of the nasopharynx; C3-5 dermatome stimulation; direct pharyngeal stimulation; direct uvular stimulation; removal of gastric contents
- Techniques leading to vagal stimulation - Iced gastric lavage; Valsalva maneuver; carotid sinus massage; digital rectal massage; digital ocular globe pressure
- Techniques interfering with normal respiratory function - Breath holding; hyperventilation; gasping; breathing into a paper bag; pulling the knees up to the chest and leaning forward; continuous positive airway pressure; rebreathing 5% carbon dioxide
- Mental distraction
- Behavioral conditioning
- Phrenic nerve or diaphragmatic pacing
Surgical intervention (typically a last resort) may include the following:
- Phrenic nerve ablation (unilateral or bilateral as appropriate)
- Microvascular decompression of the vagus nerve (according to case reports)
The term hiccup derives from the sound of the event; the alternative spelling hiccough erroneously implies an association with respiratory reflexes. Brief episodes of hiccups, which often induce annoyance in patients and merriment in observers, are a common part of life. Prolonged attacks, however, are a more serious phenomenon and often pose a diagnostic dilemma. These attacks have been associated with significant morbidity and even death.
A hiccup bout is any episode lasting more than a few minutes. Hiccups lasting longer than 48 hours are considered persistent or protracted. Hiccups lasting longer than 1 month are termed intractable. The longest recorded attack of hiccups lasted for 6 decades.
Hiccups appear to serve no purpose in humans or other mammals. Often, only a single hemidiaphragm is affected. The left hemidiaphragm is affected in 80% of cases, though bilateral involvement may occur.
Hiccups occur 4-60 times per minute until a certain number has been delivered. Typically, this is fewer than 4 or more than 30. The frequency is relatively constant for a given individual and varies inversely with arterial carbon dioxide tension (PaCO2). The loudness and rapidity of hiccups are unrelated. Hiccups are more common in the evening and may continue for a few waking hours. They occur most frequently during the first half of the menstrual cycle, especially in the few days before menstruation, and become markedly less frequent during pregnancy.
Despite centuries of contemplation, the exact pathogenesis of hiccups remains a mystery. Hippocrates and Celsus associated hiccups with liver inflammation and other conditions. Galen believed that hiccups were due to violent emotions arousing the stomach. In 1833, Shortt first recognized an association between hiccups and phrenic nerve irritation.
The hiccup reflex, originally proposed by Bailey in 1943, consists of the following:
- Afferent limb - Phrenic and vagus nerves and sympathetic chain arising from T6-12
- Hiccup center - Nonspecific location between C3 and C5
- Connections to the respiratory center, phrenic nerve nuclei, medullary reticular formation, and hypothalamus
- Efferents - Phrenic nerve (C3-5), anterior scalene muscles (C5-7), external intercostals (T1-11), glottis (recurrent laryngeal component of vagus), inhibitory autonomic processes, decreasing esophageal contraction tone, and lower esophageal sphincter tone
The cause of hiccups in children and infants is rarely found. Brief episodes in adults are usually benign and self-limiting. Typical causes include gastric distention (ie, from food, alcohol, or air), sudden changes in ambient or gastric temperature, and use of alcohol or tobacco in excess. Psychogenic causes (ie, excitement and stress) also may elicit hiccups.
Persistent or intractable episodes are more likely to result from serious pathophysiologic processes affecting a component of the hiccup reflex mechanism. More than 100 causes have been described; however, in many cases, the cause remains idiopathic.
Male predominance exists in patients with non–central nervous system (CNS)-related hiccups and those of unknown origin. About 82% of persistent or intractable episodes also occur in men. An organic cause can be identified in 93% of men and in 8% of women, resulting in an overall organic incidence of 80%; the remaining 20% of cases are considered psychogenic in origin. Psychogenic conditions associated with hiccups include the following:
- Personality disorders
- Conversion disorders
Central nervous system (CNS)-related causes of hiccups include the following:
- Structural lesions - Congenital malformations, malignancies, or multiple sclerosis
- Vascular lesions
Conditions that can give rise to diaphragmatic irritation causing hiccups are as follows:
- Hiatal hernia
- Subphrenic abscess or collection
Conditions associated with irritation of the following branches of the vagus nerve irritation can cause hiccups:
- Meningeal branches – Meningitis or glaucoma
- Auricular branches - Foreign body or hairs
- Pharyngeal branches - Pharyngitis
Procedure- or anesthesia-related causes of hiccups include the following[10, 11] :
- Hyperextension of the neck - Stretching the phrenic nerve roots
- Manipulation of the diaphragm or stomach
Metabolic causes of hiccups include the following:
Drugs associated with hiccups include the following:
- Short-acting barbiturates
Hiccups can occur at any age. They may even be observed in utero; preterm infants spend up to 2.5% of their time hiccupping. Although hiccups occur less frequently with advancing age, intractable hiccups are more common in adult life. Females develop hiccups more frequently during early adulthood than males of the same age do.
The overall incidence of hiccups is the same in males as it is in females; however, protracted and intractable hiccups occur more frequently in men (82% of cases).
In general, hiccups are self-limited, and the prognosis is excellent. The prognosis of protracted hiccups is related to that of the underlying etiology.
Protracted hiccups often are associated with underlying organic disease and often induce social and emotional distress. Therapy must address causative and complicating factors of protracted hiccups. Complications of hiccups may include the following:
- Gastroesophageal reflux
- In prolonged cases, weight loss and sleep disturbance
Wang T, Wang D. Metoclopramide for patients with intractable hiccups: a multicentre, randomised, controlled pilot study. Intern Med J. 2014 Dec. 44(12a):1205-9. [Medline].
Lee GW, Kim RB, Go SI, et al. Gender differences in hiccup patients: analysis of published case reports and case-control studies. J Pain Symptom Manage. 2015 Nov 17. [Medline].
Vanamoorthy P, Kar P, Prabhakar H. Intractable hiccups as a presenting symptom of Chiari I malformation. Acta Neurochir (Wien). 2008 Nov. 150(11):1207-8; discussion 1208. [Medline].
Krysiak W, Szabowski S, Stepien M, Krzywkowska K, Krzywkowski A, Marciniak P. Hiccups as a myocardial ischemia symptom. Pol Arch Med Wewn. 2008 Mar. 118(3):148-51. [Medline].
Morinaka S. Herpes zoster laryngitis with intractable hiccups. Auris Nasus Larynx. 2009 Oct. 36(5):606-8. [Medline].
Yeatman CF 2nd, Minoshima S. F-18 fluorodeoxyglucose PET/CT findings in active hiccups. Clin Nucl Med. 2009 Mar. 34(3):197-8. [Medline].
Celik T, Kose S, Bugan B, Iyisoy A, Akgun V, Cingoz F. Hiccup as a result of late lead perforation: report of two cases and review of the literature. Europace. 2009 Jul. 11(7):963-5. [Medline].
Zugel NP, Kox M, Lang RA, Huttl TP. Laparoscopic resection of an intradiaphragmatic bronchogenic cyst. JSLS. 2008 Jul-Sep. 12(3):318-20. [Medline].
Wilcox SK, Garry A, Johnson MJ. Novel use of amantadine: to treat hiccups. J Pain Symptom Manage. 2009 Sep. 38(3):460-5. [Medline].
Salanitri S, Goncalves AJ, Helene A Jr, Lopes FH. Surgical complications in hair transplantation: a series of 533 procedures. Aesthet Surg J. 2009 Jan-Feb. 29(1):72-6. [Medline].
Doshi H, Vaidyalingam R, Buchan K. Atrial pacing wires: an uncommon cause of postoperative hiccups. Br J Hosp Med (Lond). 2008 Sep. 69(9):534. [Medline].
Uldum B, Hallonsten AL, Poulsen S. Midazolam conscious sedation in a large Danish municipal dental service for children and adolescents. Int J Paediatr Dent. 2008 Jul. 18(4):256-61. [Medline].
Moretto EN, Wee B, Wiffen PJ, Murchison AG. Interventions for treating persistent and intractable hiccups in adults. Cochrane Database Syst Rev. 2013 Jan 31. 1:CD008768. [Medline].
Steger M, Schneemann M, Fox M. Systemic review: the pathogenesis and pharmacological treatment of hiccups. Aliment Pharmacol Ther. 2015 Nov. 42 (9):1037-50. [Medline].
Moretti R, Torre P, Antonello RM, Ukmar M, Cazzato G, Bava A. Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: a three-year follow up. Neurologist. 2004 Mar. 10(2):102-6. [Medline].
Ong AM, Tan CS, Foo MW, Kee TY. Gabapentin for intractable hiccups in a patient undergoing peritoneal dialysis. Perit Dial Int. 2008 Nov-Dec. 28(6):667-8. [Medline].
Marinella MA. Diagnosis and management of hiccups in the patient with advanced cancer. J Support Oncol. 2009 Jul-Aug. 7(4):122-7, 130. [Medline].
Turkyilmaz A, Eroglu A. Use of baclofen in the treatment of esophageal stent-related hiccups. Ann Thorac Surg. 2008 Jan. 85(1):328-30. [Medline].
Neuhaus T, Ko YD, Stier S. Successful treatment of intractable hiccups by oral application of lidocaine. Support Care Cancer. 2012 Nov. 20(11):3009-11. [Medline].
Chang CC, Chang ST, Lin JC, Li TY, Chiang SL, Tsai KC. Resolution of intractable hiccups after near-infrared irradiation of relevant acupoints. Am J Med Sci. Aug 2006. 332(2):93-6. [Medline].
Chang CC, Chang YC, Chang ST, et al. Efficacy of near-infrared irradiation on intractable hiccup in custom-set acupoints: evidence-based analysis of treatment outcome and associated factors. Scand J Gastroenterol. 2008. 43(5):538-44. [Medline].
Dietzel J, Grundling M, Pavlovic D, Usichenko TI. Acupuncture for persistent postoperative hiccup. Anaesthesia. 2008 Sep. 63(9):1021-2. [Medline].
Choi TY, Lee MS, Ernst E. Acupuncture for cancer patients suffering from hiccups: a systematic review and meta-analysis. Complement Ther Med. 2012 Dec. 20(6):447-55. [Medline].
Farin A, Chakrabarti I, Giannotta SL, Vaynman S, Samudrala S. Microvascular decompression for intractable singultus: technical case report. Neurosurgery. 2008 May. 62(5):E1180-1; discussion E1181. [Medline].
Johnson DL. Intractable hiccups: treatment by microvascular decompression of the vagus nerve. Case Report. J Neurosurg. 1993 May. 78(5):813-6. [Medline].
Naro A, Bramanti P, Calabro RS. Successful use of tetrabenazine in a patient with intractable hiccups after stroke. Pharmacotherapy. 2014 Dec. 34 (12):e345-8. [Medline].
Thompson AN, Ehret Leal J, Brzezinski WA. Olanzapine and baclofen for the treatment of intractable hiccups. Pharmacotherapy. 2014 Jan. 34 (1):e4-8. [Medline].