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Hiccups

Hiccups
Author:
Anthony J Lembo, MD
Section Editor:
Mark D Aronson, MD
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Sep 2023.
This topic last updated: Aug 08, 2022.

INTRODUCTION — Hiccups are a common and usually transient condition affecting almost everyone during their lifetime. A hiccup is also known as a “hiccough” and as a “singultus” from the Latin “singult,” meaning a "gasp" or "sob."

This topic will discuss the pathophysiology, etiology, evaluation, and treatment of hiccups.

EPIDEMIOLOGY — While brief bouts of hiccups lasting less than 48 hours are common, little is known about the overall incidence and prevalence of prolonged hiccups in the general population. However, among patients with advanced cancer, a systematic review found that 1 to 9 percent had persistent or intractable hiccups [1].

Studies show a greater prevalence of hiccups in men and in people who are taller [2-4]. In one study, the greater prevalence among males (odds ratio [OR] 2.42, 95% CI 1.40-4.17) was particularly notable in the subset of patients who did not have a central nervous system cause for their hiccups (OR 11.72, 95% CI 3.16-43.50) [5]. In a case series of 220 patients with intractable hiccups, approximately 80 percent of patients were older men [2]. No racial, geographic, or socioeconomic variation in hiccups has been documented.

PATHOPHYSIOLOGY — A hiccup occurs due to an involuntary, intermittent, spasmodic contraction of the diaphragm and intercostal muscles. This causes sudden inspiration that ends with abrupt closure of the glottis, generating the “hic” sound. The left hemidiaphragm is involved in approximately 80 percent of cases [6]. Hiccups often occur at a frequency of 4 to 60 per minute; the frequency remains relatively constant in a given individual.

The hiccup is believed to represent a reflex arc made up of several neural pathways [6]. The afferent limb includes the phrenic and vagus nerves as well as the sympathetic chain. The locus of the central mediator is not well defined; it is thought to involve interaction among the medulla oblongata and reticular formation of the brainstem, phrenic nerve nuclei, and the hypothalamus [7]; The efferent limb includes the phrenic nerve with accessory efferent neural connections to the glottis and inspiratory intercostal muscles.

The pathogenesis of hiccups lasting more than 48 hours is uncertain; in many cases, the apparent cause appears to trigger or affect a component of the putative reflex arc.

EFFECTS ON HEALTH — Although hiccups most commonly are self-limited, if they become prolonged, hiccups can decrease quality of life by interrupting eating, drinking, sleeping, and conversation; exacerbating pain; causing insomnia, fatigue, and mental stress; or adversely affecting mood. When prolonged, hiccups can have serious adverse health impacts including malnutrition, weight loss, and dehydration [8-11]. Hiccups may have other sequelae; for example, a case report described a patient with pharyngitis who developed hiccups and bouts of convulsive syncope [11].

It is unclear if hiccups have a beneficial role. In utero, hiccups may be a programmed exercise of the inspiratory muscles [12].

ETIOLOGIES — Hiccup bouts (<48 hours in duration) are typically not caused by serious disease; most people occasionally experience brief hiccups that resolve on their own in a few minutes. By contrast, hiccups lasting >48 hours occur rarely and may be caused by serious disease.

Most etiologies of prolonged hiccups are structural, infectious, or inflammatory disorders that impact either the central nervous system or the vagus or phrenic nerves or their branches. Potential causes of persistent and intractable hiccups are shown in a table (table 1).

There is a paucity of studies assessing the etiologies of hiccups. One large study of 220 patients categorized the potential causes as surgical (beginning one to four days postoperatively) or medical (including diaphragmatic hernia, cerebrovascular disease, coronary artery disease, brain disease, metabolic disease, duodenal ulcer, psychogenic and other causes) [2]. In a report of 18 cases, many patients had potentially causative comorbid conditions: vascular disease (20 percent), postoperative state (18 percent), central nervous system disease (17 percent), or duodenal ulcer (5 percent). In another case series, reflux esophagitis was the most frequent comorbidity [3]. COVID-19 has been implicated as a cause of hiccups in several case reports [13,14].

Central nervous system disorders — Central nervous system etiologies of persistent or intractable hiccups can be related to vascular, infectious, or, less commonly, other structural processes [15,16].

Hiccups have been best associated with lateral medullary infarction (Wallenberg syndrome) in which they are a relatively frequent symptom [15]. (See "Posterior circulation cerebrovascular syndromes", section on 'Lateral medullary infarction'.)

Hiccups have also been observed in patients with other pathologies in or potentially compressing the medulla including demyelinating disease [17,18], syringomyelia [19], vascular malformations [16,20], aneurysm [19,21-23], and other structural diseases [19], thus implicating the medulla as a central neurogenic mediator of hiccups. Less commonly, hiccups have been reported in patients with vascular and other brain lesions as well as with more diffuse neurologic disease [24-27]. However, a causal association in these cases can reasonably be questioned.

While hiccups may be a presenting and prominent feature of these central nervous system syndromes, they are rarely an isolated symptom.

Vagus or phrenic nerve irritation — A common precipitant of hiccups is irritation of the vagus or phrenic nerves or their branches [28,29]. Among these, gastroesophageal and postoperative causes are the most frequent.

Gastroesophageal — Gastric causes of hiccups include gastric distention, gastroesophageal reflux, gastritis, peptic ulcer disease, aerophagia, and gastric cancer [30-32]. Many cases of hiccups appear to be precipitated by gastric distention, which can occur with overeating, consumption of carbonated beverages, aerophagia (for example, due to swallowing air while chewing gum or smoking), or gastric insufflation during endoscopy [33].

Esophageal causes include esophageal distention, irritative or infectious esophagitis, and esophageal cancer [30-32]. Hiccup bouts can be induced in up to 40 percent of healthy individuals with inflation of a proximal esophageal balloon [34].

Postoperative — In the postoperative setting, where hiccups occur rarely, studies suggest an association with phrenic nerve irritation. In a retrospective review of three decades of care at a large medical center, among 40 cases of postoperative hiccups, 31 occurred after surgery along the distribution of the phrenic nerve (central nervous system [7 cases], intrathoracic [1 case], and intra-abdominal [23 cases]) [2]. Other studies have also suggested that postoperative hiccups are associated with phrenic nerve irritation, such as glottic stimulation due to intubation during general anesthesia, or visceral irritation that occurs intraoperatively [35,36].

Other irritants — Additional causes of hiccups include irritants in the head, neck, or thoracoabdominal areas.

The phrenic nerve may be irritated by abnormalities anywhere along its course from neck to diaphragm. These include goiter, tumor, cyst in the neck, a mediastinal mass, and diaphragm abnormalities. The recurrent laryngeal nerve, a branch of the vagus, may be irritated by pharyngitis, laryngitis, or by a tumor in the neck. The auricular branch may be irritated by a foreign body in the external auditory canal (eg, a hair) [37-40].

In the thoracic area, structural causes of hiccups include enlarged lymph nodes due to a neoplasm or infection, mediastinal tumors, aortic aneurysm, and chest trauma. Infectious etiologies include pneumonia, empyema, bronchitis, pleuritis, and mediastinitis. Asthma, and rarely pulmonary embolism, may cause hiccups [40-45].

Potential cardiac causes of hiccups include myocardial infarction and pericarditis [40].

In addition to gastric irritants discussed above (see 'Gastroesophageal' above), intraabdominal processes that are associated with hiccups include diaphragmatic eventration (protrusion), pancreatitis, pancreatic cancer, gallbladder disease, hepatitis, inflammatory bowel disease, and abdominal abscess [40].

Other possible precipitants of hiccup bouts include sudden changes in ambient or gastrointestinal temperature, excessive alcohol ingestion, sudden excitement, or other emotional stress [40].

Medication-induced — Use of certain medications is associated with the development of hiccups, perhaps through an effect on the central nervous system or the vagus or phrenic nerves.

Dexamethasone is a recognized cause of hiccups [46]. This drug is used for various indications including reducing chemotherapy-induced side effects. Switching from dexamethasone to methylprednisolone for patients on chemotherapy can relieve the hiccups [47,48]. (See "Overview of fatigue in palliative care", section on 'Glucocorticoids'.)

Among other medications associated with hiccups are diazepam, midazolam, barbiturates, tramadol, certain anti-cancer drugs (eg, levofolinate, fluorouracil, oxaliplatin, carboplatin, irinotecan) and alpha methyldopa [1,4,49,50].

Toxic-metabolic — Toxic-metabolic states may include hiccups as a symptom [4,49,51,52]. Examples of toxic-metabolic causes include uremia/renal impairment, hyponatremia, hypokalemia, hypocalcemia, and hypocapnia.

Psychogenic — Psychogenic factors associated with hiccups include anxiety, stress, excitement, and malingering [53]. Psychogenic causes of hiccups should be considered only after a thorough evaluation has been completed looking for other medical causes. Hiccups that persist during sleep suggest the etiology is not primarily psychogenic and may be a differentiating factor in the evaluation.

MANAGEMENT

Hiccup bouts <48 hours — The approach to hiccup bouts lasting less than 48 hours is focused on relieving symptoms. Brief hiccup bouts are typically not caused by concerning findings and thus do not require evaluation for an etiology.

Physical maneuvers — Physical maneuvers appear to terminate hiccup bouts in many patients and are simple and generally safe to perform [4]. These maneuvers are designed to interrupt normal respiratory function to cause hypercapnia, stimulate/irritate the nasopharynx or uvula, increase vagal stimulation, or relieve irritation of the diaphragm [4,54]. Examples include (table 2):

Breath holding for 5 to 10 seconds (or as tolerated).

Performing Valsalva maneuver, holding for five seconds.

Sipping on or gargling with very cold water.

Biting into a lemon.

Pulling on the tongue.

Swallowing a teaspoon of dry sugar.

Pressing gently but firmly on the eyeballs.

While sitting, pulling the knees up to the chest (or leaning forward to compress the chest); hold the position for 30 seconds to one minute if possible.

Drinking water through a rigid tube with a valve that requires significant suction effort (ie, a forced inspiratory suction and swallow tool [FISST]), which contracts the diaphragm by activating the phrenic nerve, followed by swallowing of water which activates the vagus nerve. The simultaneous activation of the two nerves is believed to be the mechanism responsible for terminating hiccups [55].

The efficacy of these maneuvers has been suggested only by case reports or observational studies and has not been confirmed. However, they are easy to perform and have low risks of complications, unless there is a contraindication (eg, recent surgery on an organ involved in the physical maneuver).

Prolonged hiccups — Hiccups continuing for 48 hours to one month are labeled “persistent” and those continuing for more than one month are called “intractable” [8].

Assessment — Hiccups lasting more than 48 hours generally warrant evaluation to look for an etiology. However, for patients with advanced malignancy, relieving symptoms with medication should be the focus, rather than extensive testing for etiologies. (See 'Pharmacotherapy' below.)

Initial assessment — For patients not known to have an advanced malignancy and who experience hiccups lasting more than 48 hours, a thorough history, physical examination, and some laboratory testing should be performed to try to determine the underlying etiology, even though in many patients a specific cause is not found [56]. Along with the initial assessment, the patient may initiate physical maneuvers; they may be helpful and are unlikely to cause harm. It is appropriate to initiate empiric therapy for symptom relief while the patient undergoes evaluation. (See 'Initial medications' below and 'Physical maneuvers' above.)

During the history, the clinician should determine how the hiccups are affecting activities of daily living (eg, eating, drinking, sleeping), obtain a complete list of medications to identify any that are associated with hiccups, elicit concomitant symptoms and evaluate for medical conditions known to be associated with hiccups, and ask about recent thoracic or abdominal surgery or general anesthesia. If the patient is taking a potentially causative medication, it should be discontinued if possible. For example, dexamethasone may be switched to methylprednisolone since dexamethasone is recognized as a cause of hiccups [47]. (See 'Medication-induced' above and 'Etiologies' above.)

The physical examination should include visualization of the external auditory canals looking for an irritant (eg, infection or foreign body), head and neck examination for thyromegaly, lymphadenopathy, or evidence of pharyngeal irritation suggestive of gastroesophageal reflux disease (GERD), neurologic examination including cranial nerve assessment, auscultation of the chest, and palpation of the abdomen for a mass.

If an etiology has not been determined by history and physical examination, laboratory testing is warranted, including electrolytes, blood urea nitrogen (BUN), creatinine, calcium, liver function tests and, if abdominal symptoms are present, amylase and lipase.

Subsequent evaluation — If an etiology is not determined during this assessment, initiating empiric pharmacotherapy is warranted. However, if there are additional signs or symptoms to evaluate, further testing is indicated (eg, evaluation of wheezing, dyspnea or abnormal imaging with chest radiography, pulmonary function testing, computed tomography (CT) scanning and/or bronchoscopy; evaluation of potential central nervous system causes with brain magnetic resonance imaging (MRI) and/or lumbar puncture; evaluation of esophageal symptoms with upper endoscopy and/or esophageal manometry). Typically, such testing is prioritized according to any suggestive features in the initial assessment. However, if hiccups are refractory to treatments and no cause has been identified, then more investigations may be required; such cases are rare.

Patients with advanced malignancy — For patients with advanced malignancy, workup is unlikely to alter management, and the cause is often multifactorial [1]. The focus for patients with advanced malignancy should be on relieving symptoms with medication, rather than on extensive evaluation for etiologies. Physical maneuvers may be tried; drug therapy should be used for treatment of hiccups lasting more than 48 hours. (See 'Physical maneuvers' above and 'Pharmacotherapy' below.)

Pharmacotherapy — Pharmacotherapy is warranted for hiccups lasting more than 48 hours, unless an etiology that can be quickly corrected is discovered during evaluation (eg, a foreign body in the external auditory canal). A variety of medication classes are used for treatment of hiccups. Most are related to the dopaminergic or GABAergic pathways [10]. Our approach is outlined in the algorithm (algorithm 1).

Treatment for prolonged hiccups (beyond simple physical maneuvers) includes medications with varying efficacy and potential for side effects, and occasionally, procedural approaches. There are insufficient randomized trials to definitively guide the choice among these treatments [57,58]. Much of the approach is based on observational studies, case reports, and small series that do not directly compare treatment options [8,59-61].

Initial medications — Initial medication may be targeted at a probable etiology or used empirically.

If an etiology for hiccups is identified and is amenable to medication, a medication from the appropriate drug class should be chosen. For example, if GERD is recognized, a proton pump inhibitor (PPI) should be initiated.

If a treatable cause for hiccups is not identified, medication may be used empirically. We suggest use of a PPI as empiric therapy and trial other agents if this is unsuccessful. However, it may also be reasonable to choose baclofen, gabapentin, or metoclopramide as first-line therapy.

A 2015 systematic review concluded that baclofen and gabapentin may be considered first-line therapy for intractable hiccups, followed by metoclopramide and chlorpromazine [62]. Although there is a paucity of robust comparative data among agents used for hiccups, baclofen and metoclopramide have shown efficacy compared with placebo in randomized controlled trials. Gabapentin has also been studied prospectively and found to be effective [62]. Other data about medications are generally from single-agent trials or case series.

The medications are available orally; for patients unable to tolerate the oral route, two of the more commonly used agents, metoclopramide and chlorpromazine, may be administered intramuscularly or intravenously, and PPIs can be given intravenously.

Specifics about initial pharmacotherapies are as follows:

Proton pump inhibitors — For GERD (proven or presumed), we suggest use of a PPI of the clinician and patient's choice, for a duration of 3-4 weeks Even in the absence of classic reflux symptoms, empiric antireflux treatment should be considered as first-line therapy, given the favorable safety profile. (See "Medical management of gastroesophageal reflux disease in adults".)

In a prospective observational study of 266 patients newly diagnosed with symptomatic GERD, 12 of whom were also experiencing hiccups, twice-daily use of a PPI was associated with resolution of the hiccups among all 12 patients [63].

Baclofen — Baclofen is used for intractable hiccups and may be considered a first-line agent, especially for central causes [10,62,64-69]. The oral dose is 5 to 10 mg three times daily, titrating to a maximum of 45 mg daily in divided doses. The most common adverse effects are drowsiness and dizziness.

Small studies have shown baclofen to be effective for hiccups. In a randomized placebo-controlled trial in 30 stroke patients with persistent hiccups, baclofen (10 mg three times daily for five days) was associated with a higher rate of hiccups cessation (relative risk [RR] = 7.0; 95% CI 1.9-25.6) [64]. In a prospective cohort study of 37 patients with and without a gastroesophageal disorder who had one or more bouts of hiccups for at least seven days; baclofen given as initial treatment produced long-term complete resolution for 18 patients and a considerable reduction of hiccups for 10 patients [66].

Baclofen is a GABA analog with a phenylethylamine moiety that acts as a receptor agonist to activate GABA, an inhibitory neurotransmitter that relaxes skeletal muscle and may block the hiccup stimulus [62,64-68].

GabapentinoidsGabapentin is a well-tolerated agent that has been used for patients experiencing hiccups while recovering from stroke or in palliative care, and it may be used as a first-line agent for patients with intractable hiccups [62,69,70]. The dose of gabapentin for hiccups ranges from 100 to 400 mg three times daily.

For refractory hiccups, gabapentin has also been used in combination with a proton pump inhibitor, baclofen, or metoclopramide [69].

In a single case report, pregabalin at a dose of 150 mg orally once daily reduced the frequency and intensity of intractable hiccups, and completely resolved them when the dose was increased to 375 mg daily [71].

Metoclopramide — Metoclopramide, a dopamine antagonist and gastric motility agent, is a treatment option for proven or presumed peripheral gastrointestinal and non-gastrointestinal etiologies of hiccups [10,69]. Initial metoclopramide dosing is 10 mg orally three or four times daily.

Potential adverse effects include extrapyramidal side effects, including tardive dyskinesia, especially at high doses and with chronic use [72]. Metoclopramide is also available for intravenous (IV) or intramuscular (IM) administration, thus can be used by patients who are unable to take oral medication.

In a randomized controlled pilot study of 36 patients, metoclopramide has been found to be effective in eliminating or improving hiccups compared with placebo (RR 2.75; 95% CI 1.09-6.94); efficacy was also noted in case series [10,73-76].

Chlorpromazine — Although chlorpromazine has been approved by the US Food and Drug Administration (FDA) for intractable hiccups and had been widely used for that purpose, it is no longer the clear first choice for hiccup treatment, due to the potential for side effects [61,77,78]. Chlorpromazine has a boxed warning about increased mortality in older adult patients who have dementia-related psychosis. Long-term use also increases the risk of tardive dyskinesia. Other potential side effects with short-term usage include hypotension, urinary retention, delirium, dystonic reactions and drowsiness. (See "Tardive dyskinesia: Etiology, risk factors, clinical features, and diagnosis", section on 'Other antiemetics'.)

For the management of intractable hiccups, chlorpromazine is started at 25 mg orally three times daily; if hiccups persist, it can be increased to 50 mg orally three times daily if tolerated. However, in older adults, and in patients in whom adverse effects develop that may be dose related (eg, hypotension, drowsiness), we use 10 mg orally three times daily. For patients with refractory hiccups that continue despite two to three days of oral treatment, or in patients unable to tolerate oral medications, chlorpromazine may be administered via an IM route. If symptoms persist after one IM dose, chlorpromazine may be administered as a single IV dose with appropriate cautions: chlorpromazine administered IV must be diluted in a large volume of saline (500 to 1000 mL saline) at a rate not to exceed 0.5 mg/minute in children and 1 mg/minute in adults. Patient must be supine during infusion and for 30 minutes after infusion to prevent hypotension.

Evidence of chlorpromazine's efficacy for hiccup treatment is available only through small case series [61,77,78].

Other medications and medication combinations — A variety of other drugs including certain anticonvulsants, antidepressants, central nervous system stimulants, and antiarrhythmics have been reported as efficacious in less rigorous studies or small case reports [58-61,68,71,79-86]. These agents include phenytoin, valproic acid, pregabalin, carbamazepine, amitriptyline, methylphenidate, quinidine, nefopam (a centrally acting nonopioid analgesic), marijuana, amantadine, oral viscous lidocaine (2%) solution, haloperidol, midazolam, nifedipine, nimodipine, orphenadrine, and levosulpiride [87].

There is a paucity of published data on concomitant use of more than one pharmacotherapy; however, a case study reported efficacy of olanzapine combined with baclofen to treat intractable hiccups refractory to multiple single agents. Although not fully understood, olanzapine’s effect on hiccups may be in part due to serotonin augmenting phrenic motoneuronal activity on reflex arcs in the spinal cord and may be related to its action as a dopamine D2-receptor antagonist [68]. Another case study has shown efficacy for the combination of lansoprazole, clonazepam, and dimenhydrinate [74].

Duration of pharmacotherapy — Most drug treatments are initiated for 5 to 10 days (with the exception of PPIs, which are continued for three to four weeks). If hiccups subside, treatment can usually be stopped the day after cessation of hiccups. If not, treatment can be continued for up to 15 days. If an agent is effective but hiccups recur after discontinuing it, longer-term usage of the agent may be needed. In some patients receiving palliative care, an indefinite duration of pharmacotherapy may be warranted.

Refractory hiccups

Medication adjustments — If the initial medication is ineffective, it is reasonable to switch therapies after three to four weeks of use, and to continue to do so, trying to find an effective therapy. For example, if hiccups are not relieved after three to four weeks of a PPI, we substitute one of the GABA analogs (baclofen or gabapentin). If after three to four weeks of baclofen or gabapentin, the patient continues to be symptomatic, we substitute metoclopramide for three to four weeks; if symptoms remain, we then switch to chlorpromazine. Other less frequently used agents may also be tried. (See 'Other medications and medication combinations' above.)

If single-agent therapy is inadequate, combination therapy is possible; however, its use depends upon the patient’s other comorbidities and tolerance to treatments.

For hiccups refractory to initial pharmacotherapies, there is not a guideline as to how many agents to try singly or in combination. If treatment of identified underlying causative disease, physical maneuvers, and pharmacotherapy titrated to patient tolerance do not sufficiently control prolonged hiccups, it is reasonable to consider complementary and alternative medicine (CAM) treatments such as acupuncture and hypnosis.

Acupuncture or hypnotherapy — The benefit of acupuncture for hiccups remains uncertain, although in systematic reviews of randomized trials acupuncture reduced hiccups in cancer patients and was possibly effective when used as an adjunct to medical therapy in stroke patients suffering from intractable hiccups [88,89]. In several observational studies, acupuncture has also been reported to improve intractable hiccups, including postoperative hiccups [90-94]. One case series reported 13 out of 16 cancer patients experienced complete remission, and the remaining three patients reported a decrease in hiccup severity with acupuncture [92].

Acupuncture is generally considered a safe procedure and has been used in a variety of other treatment settings. (See "Overview of the clinical uses of acupuncture".)

In addition, hypnosis has also been used to treat intractable hiccups [95,96].

Diaphragm-related interventions — Hiccups unrelieved by physical maneuvers or pharmacotherapy may be relieved by interventions that target the diaphragm.

There are several case reports of resolution of intractable hiccups with implantation of a vagus nerve stimulator [24,28,97,98].

A case report described five patients with intractable hiccups for up to 13 years who were successfully treated with an implantable breathing pacemaker, a device that controls excursions of the diaphragm by electrical stimulation of the phrenic nerve [99].

A case report from Korea described resolution of intractable hiccups with short-term positive pressure ventilation [100].

Surgical approaches, including phrenic nerve blocking with a local anesthetic or phrenic nerve crushing, may be successful in refractory cases [33]. It is important to assure that both hemidiaphragms are functioning prior to performing a procedure that temporarily or permanently immobilizes one hemidiaphragm. In a small series, complete remission of hiccups occurred after one, two, or three cervical epidural blocks at C3 to C5, the levels supplying the phrenic nerve [101]. Ultrasound-guided phrenic nerve block may also be effective with less morbidity than phrenic nerve crushing [102,103].

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Hiccups (The Basics)")

SUMMARY AND RECOMMENDATIONS

Pathophysiology and etiologies – A hiccup is an involuntary, spasmodic contraction of the diaphragm and intercostal muscles that results in sudden inspiration and ends with abrupt closure of the glottis. There are numerous causes of hiccups (table 1). Most frequently, hiccups are caused by gastric distention (eg, overeating, carbonated beverages). In rare cases, hiccups can be a manifestation of severe underlying disease (eg, malignancy, multiple sclerosis). (See 'Pathophysiology' above and 'Etiologies' above.)

Management – Management of hiccups depends upon the duration of symptoms and the underlying etiology, if identified.

Hiccups <48 hours – Bouts of hiccups lasting less than 48 hours are common and usually do not require medical evaluation. Physical maneuvers to interrupt normal respiratory function, such as breath holding or Valsalva maneuver, or to stimulate the nasopharyngeal/uvular area, such as sipping on or gargling with very cold water, are often effective at aborting bouts of hiccups (table 2). (See 'Hiccup bouts <48 hours' above and 'Physical maneuvers' above.)

Hiccups ≥48 hours – Hiccups lasting 48 hours or longer generally necessitate a thorough medical evaluation. Many associated conditions can be diagnosed by history and physical examination (table 1). Other diagnostic testing is indicated in select patients. Treatment should be directed toward the specific illness causing the hiccups, if known.

The patient may initiate physical maneuvers (table 2) and empiric pharmacotherapy for symptom relief while undergoing evaluation.

In patients with advanced malignancy, multiple etiologies may be contributing to hiccups, and emphasizing symptom relief rather than exhaustive evaluation may be beneficial. (See 'Assessment' above and 'Physical maneuvers' above and 'Pharmacotherapy' above.)

For patients with prolonged hiccups that cannot be aborted with physical maneuvers (table 2), we suggest initiating pharmacologic treatment with a proton pump inhibitor (PPI) (Grade 2C). Reasonable alternative first-line agents include baclofen, gabapentin, and metoclopramide (algorithm 1). (See 'Pharmacotherapy' above.)

Acupuncture and surgery are additional treatment options if hiccups fail to respond to physical maneuvers and drug therapy. (See 'Acupuncture or hypnotherapy' above and 'Diaphragm-related interventions' above.)

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Topic 6892 Version 42.0

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