Background    Hiccups (singultus) are an involuntary reflex involving the respiratory muscles of the chest and diaphragm, mediated by the phrenic and vagus nerves and a central (brainstem) reflex center.  A single episode can last for a few seconds to as long as several days.  When they last longer than 48 hours, hiccups are termed persistent; longer than one month, intractable.  Persistent and intractable hiccups can be very distressing to patients and families and diminish quality of life.  Etiologies range in seriousness from stress/excitement, gastric or esophageal distention, corticosteroids, idiopathic, post-surgical, chemotherapy, cancer, myocardial infarction, liver disease, uremia, and CNS lesions.  Irritation of the vagus nerve or diaphragm is a common pathophysiologic mechanism.

Management    Once hiccups have lasted beyond a time-limited annoyance, deciding on therapeutic intervention should be based on a thorough clinical assessment and, if possible, treatment directed at the underlying cause.  A thorough history, review of medications, focused review of systems, and physical exam may help guide initial choice of treatment.  Many drug and non-drug treatments have been used, but there is little evidence of any one superior approach to management. The patient’s prognosis, current level of function, and potential adverse effects from any proposed treatment should be considered.

Non-Pharmacological Therapy In most clinical scenarios, it is best to start with non-pharmacologic therapy and resort to pharmacologic options for refractory cases. There are many time-honored home remedies — gargling with water, biting a lemon, swallowing sugar, or producing a fright response – which are low risk even if they are lacking in evidence.  Other non-pharmacologic options include:

• Supra-supramaximal inspiration (SSMI): a case series demonstrated 84% success among 19 patients by utilizing this breathing technique. With SSMI, the patient exhales completely, then inhales a deep breath; waits 10 seconds and without exhaling, inhales a little more; waits another five seconds, aims to breathe in a little more again before finally exhaling. 
• Use of a specially designed suction device (HiccAway®) has shown positive results in a prospective trial.  It is designed like a straw with a pinhole size opening on the bottom and a larger opening on top to generate enough diaphragmatic pressure to disrupt phrenic and vagus nerve communication.
• Interrupting the respiratory cycle through sneezing, coughing, breath holding, hyperventilation, or breathing into a paper bag.
• Vagal stimulation such as carotid massage or valsalva maneuver.
• Interruption of phrenic nerve transmission via rubbing over the 5^th cervical vertebrae

Pharmacologic Therapy

• Anti-Psychotics:  Chlorpromazine – the only FDA approved drug for hiccups. Dose:  25-50 mg PO TID or QID. Can also be given by slow IV infusion (25-50 mg in 500-1000 ml of NS over several hours).  Haloperidol – a useful alternative to chlorpromazine; give a 2-5 mg (SubQ/PO) loading dose followed by 1-4 mg PO TID.
• Anti-Convulsants:  Gabapentin – at doses of 300-400 TID has been described as effective in multiple case reports. Its dual role as an analgesic may make it an especially attractive therapeutic agent.  Phenytoin – reportedly effective in patients with a CNS etiology of their hiccups.  Dose: 200 mg slow IV push followed by 300 mg PO daily. Others: Valproic Acid and Carbamazepine have been reported to work for selected patients. 
• Miscellaneous:  Baclofen – the only drug studied in a double blind randomized controlled study for treatment of hiccups.  5 mg PO q8 hours did not eliminate hiccups but did provide symptomatic relief in some patients.  Metoclopramide – 10 mg PO QID is an option, especially if stomach distension is the etiology.  Nifedipine – 10 mg BID with gradual increase up to 20 mg TID has been suggested as a relatively safe alternative if other interventions have failed. Other drugs that have been tried with very limited success include: amitriptyline, sertraline, inhaled lidocaine, ketamine, edrophonium, methylphenidate, and amantidine.

Interventions: Acupuncture, diaphragmatic pacing electrodes, or surgical ablation of the reflex arc can be considered when other treatments fail.

References

1. Kolodzik PW, Eilers, MA.  Hiccups (singultus):  review and approach to management.  Ann Emerg Med. 1991; 20:565-573.
2. Lewis J.  Hiccups: causes and cures.  J Clin Gastro. 1985; 7:539-552.
3. Rousseau, P.  Hiccups.  Southern Med J. 1995; 2:175-181.
4. Bondi N, Bettelli, A.  Treatment of hiccup by acupuncture in patients under anesthesia and in conscious patients.  Minerva Med. 1981; 72:2231-2234.
5. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a double-blind, randomized, controlled, cross-over study.  A J Gastro. 1992; 87:1789-91.
6. Physicians’ Desk Reference.  61^st Edition. Thomson PDR; 2007.  Available at http://pdr.net. 
7. Smith HS, Busracamwongs A.  Management of hiccups in the palliative care population.  Am J Hosp Pall Care. 2003; 20:149-54.
8. Vaidya V. Sertraline in the treatment of hiccups.  Psychosomat. 2000; 41:353-355.
9. Hernandez JL, et al.  Gabapentin for intractable hiccup. Am J Med. 2004; 117:279-81.
10. Marinella, Mark A. “Diagnosis and management of hiccups in the patient with advanced cancer.” J support Oncol 7.4 (2009): 122-7.
11. Wilcox SK, Garry A, Johnson MJ.  Novel use of amantadine to treat hiccups.  Journal of Pain and Symptom Management 2009; 38: 460-5.  Volume 38, Issue 3, September 2009, Pages 460–465.
12. Morris LG, Marti JL, Ziff DJ. Letter to editor: Termination of idiopathic persistent singultus (hiccup) with supra-supramaximal inspiration. Anesthesia and Analgesia 2004; 99(1):305.
13. Alvarez J, Anderson JM, Snyder PL.  Evaluation of the forced inspiratory suction and swallow tool to stop hiccups.  JAMA Netw Open 2021; 4(6):e2113933.

Conflicts of Interest: none to report
Version History:  This Fast Fact was originally edited by David E Weissman MD. 2^nd
Edition was edited by Drew A Rosielle and published October 2007; 3^rd Edition June 2015; 4^th edition in February 2023 by Sean Marks MD.