Hiccups
Hiccups - Summary
Hiccups involve a sudden, involuntary (reflex), usually unilateral, diaphragmatic contraction causing sudden inspiration. The incoming air is stopped by closure of the glottis which produces the characteristic sound. Hiccups do not appear to perform any useful or protective function.
Hiccups are usually transient, lasting less than 48 hours.
Persistent or protracted hiccups last between 48 hours and 1 month.
Intractable hiccups last for more than 1 month.
Persistent and intractable hiccups are rare, but may cause complications (e.g. fatigue, weight loss, wound dehiscence).
If hiccups have lasted more than 48 hours, a full assessment should be performed to assess whether there is an underlying cause. This usually requires referral to secondary care. Baseline investigations that may be considered in primary care include:
Full blood count (anaemia may indicate gastrointestinal pathology).
Erythrocyte sedimentation rate or C-reactive protein level (an elevated level suggests the presence of an underlying disease).
Urea and electrolytes, creatinine (to exclude uraemia, hyponatraemia, hypokalaemia).
Blood glucose (to exclude hyperglycaemia).
Liver function tests (abnormal results may indicate hepatitis, liver metastases).
Serum calcium (to exclude hyper- or hypocalcaemia).
Electrocardiogram (to exclude pericarditis, recent myocardial infarction).
Chest radiograph (to exclude lung pathology).
The management of a short episode of hiccups involves offering reassurance that hiccups are likely to resolve spontaneously, and suggesting the following:
Stimulation of the nasopharynx: sipping iced water, swallowing granulated sugar, tasting vinegar, biting on a lemon.
Interruption of normal respiratory function: Valsalva manoeuvre, breath holding, hyperventilating, breathing into a paper bag, sneezing.
Counter-irritation of the diaphragm: pulling the knees up to the chest, leaning forward to compress the chest.
The person should return if their hiccups have not resolved in 48 hours or if they recur frequently.
The management of persistent or intractable hiccups involves:
Referral to secondary care for further assessment or treatment of the underlying cause, unless it can be easily diagnosed and managed in primary care.
While awaiting referral, advice should be offered on physical manoeuvres and consideration given to prescribing drug treatment.
For symptom relief, drugs which can be considered in adults with persistent hiccups include:
Chlorpromazine — should be avoided in a palliative care situation because of its potential adverse effects.
Haloperidol.
Baclofen (off-label indication) — may be particularly useful when other drugs have failed.
Metoclopramide (off-label indication) — may be particularly useful if hiccups due to gastric stasis or distension.
Gabapentin (off-label indication) — may be effective if the hiccups have a neurological cause.
Midazolam (off–label indication) — should be considered only on specialist advice in the terminal phase of advanced cancer if the person is very distressed.
A drug should be tried for 2 weeks, increasing the dosage until hiccups are controlled, until adverse effects prove troublesome, or until the maximum recommended dosage is reached.
If effective, a reduction of the dose and stopping the drug should be tried.
If ineffective or not tolerated, a different drug should be considered.
Have I got the right topic?
This CKS topic covers the management of transient, persistent, and intractable hiccups (also called 'hiccoughs' or 'singultus').
This CKS topic does not cover the use of drug treatments for intractable hiccups in children.
There is a separate CKS topic on Dyspepsia - unidentified cause.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
November 2012 — minor update. The links to the electronic medicines website (www.medicines.org.uk) have been updated.
September 2012 — reviewed. A literature search was conducted in September 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No changes to clinical recommendations have been made.
Previous changes
July to November 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
There have been minor changes to the section on recommended drugs and dosages.
June 2005 — reviewed. Validated in September 2005 and issued in November 2005.
January 2002 — reviewed. Validated in March 2002 and issued in April 2002.
October 1998 — written, replacing guidance on Hiccough and Psychogenic hiccough.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 September 2012.
HTAs (Health Technology Assessments)
No new HTAs since 1 September 2012.
Economic appraisals
No new economic appraisals relevant to England since 1 September 2012.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Choi, T.Y., Lee, M.S., and Ernst, E. (2012) Acupuncture for cancer patients suffering from hiccups: a systematic review and meta-analysis. Complementary Therapies in Medicine 20(6), 447-455. [Abstract]
Moretto, E.N., Wee, B., Wiffen, P.J., and Murchison, A.G. (2013) Interventions for treating persistent and intractable hiccups in adults (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Primary evidence
No new randomized controlled trials published in the major journals since 1 September 2012.
New policies
No new national policies or guidelines since 1 September 2012.
New safety alerts
No new safety alerts since 1 September 2012.
Changes in product availability
No changes in product availability since 1 September 2012.
Goals and outcome measures
Goals
Appropriate treatment of hiccups in primary care settings
Appropriate referral to secondary care or other specialist service
Providing appropriate advice to patients
Background information
Definition
What is it?
Hiccups involve a sudden, involuntary (reflex), usually unilateral, diaphragmatic contraction causing sudden inspiration. The incoming air is stopped by closure of the glottis which produces the characteristic sound. Hiccups do not appear to perform any useful or protective function, unlike other reflexes [Lewis, 2000; Schuchmann and Browne, 2007].
Hiccups are usually transient, lasting less than 48 hours [Cymet, 2002].
Persistent or protracted hiccups last between 48 hours and 1 month.
Intractable hiccups last for more than 1 month.
Risk factors
What are the risk factors?
There is no major difference in the occurrence of transient hiccups in men and women. However, persistent and intractable hiccups occur more frequently in men [Rousseau, 1995].
Importance
What are they important?
Persistent and intractable hiccups are rare, but may cause complications (e.g. fatigue, weight loss, wound dehiscence), and may indicate an underlying disease process or injury [Howard, 1992; Friedman, 1996; Cymet, 2002].
Diagnosis
Diagnosis of hiccups
Assessment for an underlying cause
How should I assess a person with persistent or protracted hiccups for an underlying cause?
If hiccups have lasted more than 48 hours, perform a full assessment to assess whether there is an underlying cause.
Exclude a possible underlying cause based on history and clinical findings. This usually requires referral to secondary care, but baseline investigations that may be considered in primary care include:
Full blood count (anaemia may indicate gastrointestinal pathology).
Erythrocyte sedimentation rate or C-reactive protein level (an elevated level suggests the presence of an underlying disease).
Urea and electrolytes, creatinine (to exclude uraemia, hyponatraemia, hypokalaemia).
Blood glucose (to exclude hyperglycaemia).
Liver function tests (abnormal results may indicate hepatitis, liver metastases).
Serum calcium (to exclude hyper- or hypocalcaemia).
Electrocardiogram (to exclude pericarditis, recent myocardial infarction).
Chest radiograph (to exclude lung pathology).
Additional information
Additional information
Many causes of hiccups have been reported, including:
Abdominal: gastric distension, gastric reflux, gastritis, small bowel obstruction, cholecystitis, subphrenic abscess.
Head and neck: tumour, cyst, goitre, pharyngitis, irritation of tympanic membrane (e.g. by a foreign body).
Thorax: tumours, pneumonia, pericarditis, myocardial infarction, aortic aneurysm.
Central nervous system: trauma, infection (e.g. cerebral abscess, encephalitis), stroke, tumours, multiple sclerosis.
Metabolic: uraemia, hypokalaemia, hypocalcaemia, hyperventilation, uncontrolled diabetes mellitus, alcohol, Addison's disease.
Surgical: anaesthesia, neck extension, post-operative (intra-abdominal, thoracotomy, craniotomy).
Psychogenic: stress, excitement, reaction to bereavement (grief), anorexia nervosa, malingering.
Drugs: corticosteroids, benzodiazepines, barbiturates, opioids, methyldopa.
[Lewis, 1985; Howard, 1992; Launois et al, 1993; Rousseau, 1995; Cymet, 2002; Smith and Busracamwongs, 2003]
Basis for recommendation
Basis for recommendation
CKS recommends a full assessment of a person with prolonged hiccups, because this often indicates an underlying cause [Launois et al, 1993; Schuchmann and Browne, 2007]. In a retrospective study, hiccups lasting more than 48 hours were more likely to be associated with an organic or anatomic cause [Cymet, 2002].
A study of causative factors in people with intractable hiccups (study duration almost 30 years) found that 93% of 181 males had organic disease and 92% of 36 females had psychogenic hiccups [Souadjian and Cain, 1968].
The suggestion of which investigations to consider is based on discussion in review articles [Kolodzik and Eilers, 1991; Rousseau, 1995].
Management
Management
Scenario: Management: covers the management of people with hiccups.
Scenario: Management
Scenario: Management of hiccups
Management of short episode of hiccups
How should I manage a short episode of hiccups?
Reassure the person that their hiccups are likely to resolve spontaneously.
Consider suggesting physical manoeuvres if these have not already been tried. These include:
Stimulation of the nasopharynx: sipping iced water, swallowing granulated sugar, tasting vinegar, biting on a lemon.
Interruption of normal respiratory function: Valsalva manoeuvre, breath holding, hyperventilating, breathing into a paper bag, sneezing.
Counter-irritation of the diaphragm: pulling the knees up to the chest, leaning forward to compress the chest.
Advise the person to return if their hiccups have not resolved in 48 hours or if they recur frequently, and consider referral.
Basis for recommendation
Basis for recommendation
Short bouts of hiccups are mostly associated with gastric distension or alcohol intake, and usually resolve spontaneously without requiring medical attention [Launois et al, 1993]. Treatment other than simple physical manoeuvres is rarely needed [Lewis, 1985].
The suggested physical manoeuvres were included in reviews [Rousseau, 1995; Lewis, 2000] but are based on anecdotal reports rather than trial evidence [Lewis, 1985].
People should be advised to return for further assessment if hiccups are prolonged because this often indicates an underlying disease process or injury [Launois et al, 1993; Schuchmann and Browne, 2007]. In a retrospective study, hiccups lasting more than 48 hours were more likely to be associated with an organic or anatomic cause [Cymet, 2002].
CKS found no evidence to guide management of recurrent episodes of hiccups.
Management of persistent or protracted hiccups
How should I manage persistent or intractable hiccups?
Refer to secondary care for further assessment or treatment of the underlying cause, unless it can be easily diagnosed and managed in primary care. Which specialist to refer to, and the urgency of referral, will depend on the suspected underlying cause.
While the person is waiting to be referred:
Advise on physical manoeuvres, if they have not already been tried.
Consider prescribing drug treatment for adults if physical manoeuvres are not effective.
Seek specialist advice if drug treatment is being considered for a child.
In a palliative care situation, referral may not be appropriate where hiccups are known to be a complication of cancer (e.g. gastric distension). If the hiccups are difficult to control with drug treatment, seek advice from a palliative care specialist.
Basis for recommendation
Basis for recommendation
Referral
CKS recommends referral of people with prolonged hiccups because:
Prolonged duration of hiccups often indicates an underlying disease process or injury [Launois et al, 1993; Schuchmann and Browne, 2007]. In a retrospective study, hiccups lasting more than 48 hours were more likely to be associated with an organic or anatomic cause [Cymet, 2002].
Prolonged hiccups can cause a number of complications, including insomnia, depression, weight loss, wound dehiscence, and exhaustion [Launois et al, 1993].
Regarding choice of specialist, CKS advises clinical judgement based on the assessment findings because of the wide range of conditions which may cause hiccups.
Physical manoeuvres
The suggested physical manoeuvres were included in reviews [Rousseau, 1995; Lewis, 2000] but are based on anecdotal reports rather than trial evidence [Lewis, 1985].
Drug treatment
Drug treatment is suggested as an option because hiccups are a disabling symptom that can cause a number of complications, and are unlikely to resolve spontaneously if the episode has a duration of more than a week [Launois et al, 1993].
Review articles suggest that for people in whom the cause cannot be identified or treated, general measures and empiric treatments may be necessary [Rousseau, 1995; Smith and Busracamwongs, 2003].
Drug treatment
What drugs should I consider?
Children
Seek specialist advice if drug treatment is being considered for a child.
Adults
If a person has symptoms suggestive of gastro-oesophageal reflux and has no upper gastrointestinal alarm symptoms, consider a trial course of a proton pump inhibitor (see the CKS topic on Dyspepsia - unidentified cause).
For symptom relief, consider the following drugs in primary care (taking into account the licensed indication and the number of case reports of effectiveness):
Chlorpromazine (licensed) — avoid in a palliative care situation because of its potential adverse effects.
Haloperidol (licensed).
Baclofen (off-licence indication) — may be particularly useful when other drugs have failed.
Metoclopramide (off-licence indication) — may be particularly useful for people with hiccups due to gastric stasis or distension.
Gabapentin (off-licence indication) — may be effective if the hiccups have a neurological cause. Use with caution in people with renal impairment and the elderly.
Midazolam (off–licence indication) — consider only on specialist advice in the terminal phase of advanced cancer if the person is very distressed by the hiccups.
Suggested dosages for use in primary care are outlined in Table 1. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (www.medicines.org.uk) or the British National Formulary (BNF) (www.bnf.org).
Try a drug for 2 weeks, increasing the dosage until hiccups are controlled, until adverse effects prove troublesome, or until the maximum recommended dosage is reached.
If this is effective, try reducing the dose and stopping the drug. If hiccups recur, increase the dose again or restart the drug if it was stopped.
If the drug is not effective or is not tolerated, consider trying a different drug while awaiting referral.
Additional information
Additional information
| Drug | Suggested dosages for use in primary care |
|---|---|
| Chlorpromazine* | 25–50 mg three to four times a day. |
| Haloperidol* | 1.5 mg up to three times a day (a once-daily dose is usually sufficient as haloperidol has a long half-life); usual maintenance dose 1.5 mg to 3.0 mg at night. |
| Baclofen†‡ | 5 mg three times a day, increased to 20 mg three to four times a day if necessary. |
| Gabapentin† | 400 mg three to four times a day for 3 days, then 400mg once daily for 3 days (slower titration and dose adjustment may be required in people with renal impairment, or the elderly or frail). |
| Metoclopramide† | 10 mg three times a day. |
| Midazolam‡ | Seek specialist palliative care advice. |
Basis for recommendation
Basis for recommendation
Choice of drug
Medication is often used for prolonged hiccups [Cymet, 2002], but there is no strong evidence to guide the choice of drug. CKS only identified one randomized controlled trial of treatment for hiccups (a crossover trial of four people treated with either baclofen or placebo) [Ramirez and Graham, 1992]. There are, however, numerous case reports of the effectiveness of drugs in the treatment of hiccups. CKS has recommended the following drugs taking into account the licensed indication and the number of case reports of effectiveness.
A proton pump inhibitor may be effective in relieving symptoms if hiccups are related to gastro-oesophageal reflux disease [Smith and Busracamwongs, 2003; Schuchmann and Browne, 2007].
Chlorpromazine is licensed for the treatment of intractable hiccups. It may be less effective when initiated in primary care, as the main report demonstrating effectiveness used intravenous administration until the hiccups were controlled before switching to oral treatment [Friedgood and Ripstein, 1955]. Adverse effects (particularly sedation) frequently limit its usefulness, particularly in the palliative care situation.
Haloperidol is licensed for the treatment of intractable hiccups. Most reports of its effectiveness described intramuscular administration, followed by oral treatment [Ives et al, 1985]. It is better tolerated than chlorpromazine and can be used in palliative care [Finnish Medical Society, 2007].
Baclofen (unlicensed indication) is commonly regarded as a first-line drug [DTB, 1990;]. There are numerous case reports documenting its effectiveness, particularly when other drugs have failed [Burke et al, 1988; Lance and Bassil, 1989; Yaqoob et al, 1989; Bhalotra, 1990; Ramirez and Graham, 1992; Fodstad and Nilsson, 1993; Guelaud et al, 1995; Johnson and Kriel, 1996; D'Alessandro and Dever, 1997; Marien and Havlak, 1997; Marino, 1998; Walker et al, 1998; Oneschuk, 1999; Katsinelos et al, 2000; Lewis, 2000; Hadjiyannacos et al, 2001]. Review guidelines [Finnish Medical Society, 2007; ICSI, 2007] and the Palliative Care Formulary [Twycross and Wilcock, 2011] also suggest that baclofen has a role in people with hiccups in palliative care [Regnard, 2010]
Metoclopramide (unlicensed indication) has been reported to stop hiccups regardless of the underlying cause [Middleton, 1973; Madanagopolan, 1975], but may be particularly helpful in people with gastric stasis or distension. One case report found it to be effective for migraine-associated hiccups [Gupta, 2006]. Metoclopramide is also an option for use in palliative care [Finnish Medical Society, 2007].
Gabapentin (unlicensed indication) has been reported to be effective in the treatment of hiccups, particularly if they are thought to have a neurological cause (e.g. stroke) [Petroianu et al, 2000; Porzio et al, 2003; Hernandez et al, 2004; Moretti et al, 2004; Alonso-Navarro et al, 2007]. A case series illustrated the role of gabapentin when adverse effects limited the use of other medications [Schuchmann and Browne, 2007]. A review including three of these case reports concluded that gabapentin may be also be useful in palliative care because it is not metabolized by the liver (so therefore could be considered for people with liver failure), has few adverse effects, and does not cause sedation [Tegeler and Baumrucker, 2008].
Parenteral midazolam may be appropriate in the terminal phase of advanced cancer if other treatments are unsuccessful and if the person is very distressed by the hiccups, but should only be used on the advice of a specialist [Wilcock and Twycross, 1996; Moro et al, 2005; Regnard and Dean, 2010; Twycross and Wilcock, 2011].
Drugs not included
Other (unlicensed) options have been mentioned in case reports including amitriptyline [Stalnikowicz et al, 1986; Parvin et al, 1988; Peabody et al, 1988], carbamazepine [McFarling and Susac, 1974], valproic acid [Jacobson et al, 1981], sodium valproate [Masand et al, 1990; Regnard and Dean, 2010], and nifedipine [Mukhopadhyay et al, 1986; Lipps et al, 1990; Brigham and Bolin, 1992]. However, given the relatively smaller body of evidence to support their use and their comparative adverse effect profiles, CKS does not recommend that they are used to treat intractable hiccups in primary care.
Dose
The recommended dosages of the licensed drugs (chlorpromazine and haloperidol) are based on the British National Formulary [BNF 64, 2012], the Summary of Product Characteristics for each drug [ABPI Medicines Compendium, 2011; ABPI Medicines Compendium, 2012], and the Palliative Care Formulary [Twycross and Wilcock, 2011].
For the unlicensed drugs, there is no manufacturer information, therefore CKS has based recommended dosages on those used in the relevant case reports. For baclofen and midazolam, recommended dosages were also guided by the Palliative Care Formulary [Twycross and Wilcock, 2011].
Duration of treatment
The duration of treatment reported in the literature varies considerably, ranging from 1 week to several months.
Many people who were treated for only short periods, with cessation of their hiccups, remained free of hiccups on discontinuation of treatment. However, there are also reports of people who relapsed as soon as treatment was withdrawn and who had to go back on treatment, often having to stay on treatment for several months.
The strategy recommended by CKS is pragmatic advice, allowing the clinician to adjust the dose and duration according to the person's response.
Evidence
Evidence
Supporting evidence
Evidence on drug treatment of hiccups
There is a lack of trial evidence to support the use of drug treatment for hiccups.
CKS only identified one randomized controlled trial of a treatment for hiccups (a crossover trial of four people treated with either baclofen or placebo) [Ramirez and Graham, 1992]. The results should be interpreted with caution, given the small number of trial participants, the subjective nature of the assessment of the severity of hiccups, and the potential for inaccuracy in the measurement of frequency of hiccups.
Four men with intractable hiccups, who had previously tried a number of medications without improvement, were given either oral baclofen 5 mg or placebo every 8 hours for 3 days, and then the dose was doubled for a further 3 days. The dose was reduced to stop over a week, and after a further week's washout period the intervention was repeated as a crossover.
Nursing staff evaluated the frequency of hiccups (for 10 minutes at nine daily time points) and their severity, and the participants also rated the severity of their own hiccups.
When baclofen was taken, the hiccup-free period increased by 69% with the 15 mg daily dosage (p = 0.08), and by 120% with the 30 mg daily dosage (p = 0.003). With placebo, the hiccup-free period stayed the same or worsened.
In terms of overall improvement, the mean improvement was 22.5 +/– 3.4% with the 15 mg per day dosage, and 31.4 +/– 4.8% with the 30 mg per day dosage.
Search strategy
Scope of search
A literature search was conducted for guidelines and systematic reviews on the primary care management of hiccups.
Search dates
March 2007 - September 2012
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp Hiccup/, hiccup$.tw, singlutus.tw
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSh subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
Royal College of General Practitioners
National Guidelines Clearinghouse
Guidelines International Network
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
Institute for Clinical Systems Improvement
National Health and Medical Research Council (Australia)
Royal Australian College of General Practitioners
British Columbia Medical Association
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Driver and Vehicle Licensing Agency
NHS Health at Work (occupational health practice)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
Patient experiences
Patient.co.uk - Patient Support Groups
Sources of medicines information
The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (BNF)
electronic Medicines Compendium (eMC)
European Medicines Agency (EMEA)
References
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