You are in: eMedicine Specialties > Emergency Medicine > GASTROINTESTINAL HiccupsArticle Last Updated: Aug 2, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Garry Wilkes, MBBS, Director, Emergency Medicine, Adjunct Associate Professor, Edith Cowan University, Department of Emergency Medicine, Bunbury Health Service Editors: Robin R Hemphill, MD, MPH, Associate Professor, Director, Disaster Preparedness, Department of Emergency Medicine, Vanderbilt University Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eugene Hardin, MD, FACEP, FAAEM, Chair and Associate Professor, Department of Emergency Medicine, Charles R Drew University of Medicine and Science; Chair, Department of Emergency Medicine, Martin Luther King, Jr/Drew Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School Author and Editor Disclosure Synonyms and related keywords: hiccups, hiccoughs, singultus, gastric distention, alcohol, tobacco, excitement, stress, phrenic nerve irritation INTRODUCTIONSection 2 of 11
  BackgroundThe term "hiccup" derives from the sound of the event. "Hiccough" erroneously implies an association with respiratory reflexes. The medical term, singultus, is thought to have originated from the Latin, singult, which translates roughly as "the act of catching one's breath while sobbing." Brief episodes of hiccups, which often induce annoyance in patients and merriment in observers, are a common part of life. Prolonged attacks are a more serious phenomenon and often 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. If hiccups last longer than 48 hours, they are considered persistent or protracted. Hiccups lasting longer than one month are termed intractable. The longest recorded attack is 6 decades. PathophysiologyHiccups appear to serve no purpose in humans or other mammals. Often, only one hemidiaphragm is affected. The left hemidiaphragm is affected in 80% of cases, although 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 PCO2. Loudness and rapidity of hiccups are unrelated. Hiccups are more common in the evening and may continue for a few waking hours. Hiccups occur most frequently during the first half of the menstrual cycle, especially in the few days before menstruation, and decrease markedly during pregnancy. The exact cause remains a mystery despite centuries of contemplation. Hippocrates and Celsus associated hiccups with liver inflammation and other conditions. Galen believed 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:
SexOverall incidence of hiccups is equal between males and females; however, protracted and intractable hiccups occur more frequently in men (82% of cases). AgeHiccups occur at any age and 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. CLINICALSection 3 of 11
HistoryMedical training is not required to diagnose hiccups. Brief episodes that self-terminate or that respond to simple maneuvers need no investigation or follow-up care. In contrast, persistent and intractable hiccups frequently are associated with an underlying pathological process and may induce significant morbidity. The focus of the history, examination, and investigation is to identify these causes and effects.
PhysicalA full physical examination is necessary. Considering the wide range of differentials, a complete and focused physical examination may yield evidence of the following:
CausesThe cause of hiccups in children and infants rarely is found. Brief episodes in adults usually are benign and self-limiting. Typical causes include gastric distention (ie, food, alcohol, air), sudden changes in ambient or gastric temperature, and use of alcohol and/or tobacco in excess. Psychogenic causes (ie, excitement, stress) also may elicit hiccups. Persistent or intractable episodes are more likely to result from serious pathophysiological processes affecting a component of the hiccup reflex mechanism. More than 100 causes have been described; however, in many cases, the cause remains idiopathic. These may be classified as follows:
DIFFERENTIALSSection 4 of 11
Acute Renal Failure Anxiety Appendicitis, Acute Asthma Brain Abscess Bronchitis Cholecystitis and Biliary Colic Diaphragmatic Injuries Encephalitis Epidural and Subdural Infections Esophagitis Foreign Bodies, Ear Gastroenteritis Glaucoma, Acute Angle-Closure Hepatitis HIV Infection and AIDS Hypocalcemia Hypokalemia Hyponatremia Inflammatory Bowel Disease Meningitis Multiple Sclerosis Myocardial Infarction Myocarditis Neoplasms, Brain Neoplasms, Lung Pancreatitis Pericarditis and Cardiac Tamponade Pneumonia, Aspiration Pneumonia, Bacterial Pneumonia, Empyema and Abscess Pneumonia, Immunocompromised Pneumonia, Mycoplasma Pneumonia, Viral Toxicity, Alcohols Toxicity, Caustic Ingestions Uremia
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| Drug Name | Chlorpromazine (Thorazine) |
|---|---|
| Description | DOC; antidopaminergic drug; blocks postsynaptic mesolimbic dopamine receptors; has anticholinergic effect; can depress the reticular activating system (possibly all are responsible for relieving nausea and vomiting); blocks alpha-adrenergic receptors; depresses release of hypophyseal and hypothalamic hormones. |
| Adult Dose | 25-50 mg PO tid/qid; slow IV infusion with patient lying flat when symptoms persist; 25-50 mg in addition to 500-1000 mL of saline (monitor blood pressure); 25-50 mg IM if symptoms persist for 2-3 d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease; circulatory collapse; CNS depression; pheochromocytoma |
| Interactions | Other CNS depressants, anticholinergics, or anticonvulsants; antihypertensives may cause additive effect; coadministration with epinephrine may cause hypotension |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | May cause pseudoparkinsonism; akathisia is a common extrapyramidal reaction in elderly persons; lowers seizure threshold and increases risk of seizures in patients with history of seizures |
| Drug Name | Metoclopramide (Reglan) |
|---|---|
| Description | Blocks dopamine receptors in the chemoreceptor trigger zone of CNS. |
| Adult Dose | 10-20 mg PO tid/qid for 7 d |
| Pediatric Dose | 1-2 mg/kg PO tid/qid for 7 d |
| Contraindications | Documented hypersensitivity; pheochromocytoma; GI hemorrhage; obstruction or perforation of bowels; seizure disorders |
| Interactions | May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution in history of mental illness and Parkinson disease |
These agents are used for severe muscle spasms.
| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | Inhibits spread of motor activity by acting in motor cortex. |
| Adult Dose | 15-20 mg/kg IV loading dose followed by a maintenance dose of 2-3 mg/kg PO bid; individualize further doses per blood levels and tolerability if chronic dosing required |
| Pediatric Dose | 15-20 mg/kg PO/IV loading dose once or in divided doses, followed by an initial dose of 5 mg/kg/d PO/IV divided bid/tid and a maintenance dose of 4-8 mg/kg PO/IV divided bid/tid |
| Contraindications | Documented hypersensitivity; sinoatrial block, sinus bradycardia, second-degree and third-degree AV block, or Adams-Stokes syndrome (because of effect on ventricular automaticity) |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase phenytoin toxicity Phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Perform blood counts and urinalyses at the beginning of therapy and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if rash appears; if rash is exfoliative, bullous, or purpuric, do not resume use; death from cardiac arrest after too rapid IV administrations (sometimes preceded by marked QRS widening); caution with acute intermittent porphyria; caution with diabetes (may raise blood sugar levels); discontinue drug if hepatic dysfunction occurs |
| Drug Name | Valproic acid (Depakote, Depakene) |
|---|---|
| Description | Although mechanism of action is not established, activity may be related to increased brain levels of gamma-aminobutyric acid (GABA), or enhanced GABA action. Valproate may also potentiate postsynaptic GABA responses, affect potassium channel, or have a direct membrane-stabilizing effect. |
| Adult Dose | 10-15 mg/kg/d PO in 1-3 divided doses |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; hepatic disease/dysfunction |
| Interactions | Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Thrombocytopenia and abnormal coagulation parameters have occurred; the risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness |
| Drug Name | Carbamazepine (Tegretol) |
|---|---|
| Description | May block post-tetanic potentiation by reducing summation of temporal stimulation. |
| Adult Dose | 200 mg PO bid (100 mg PO qid if susp) |
| Pediatric Dose | <6 years: 10-20 mg/kg/d PO bid/tid (qid with susp) 6-12 years: 100 mg PO bid (50 mg qid of susp) >12 years: Administer as in adults, not to exceed 1000 mg/d in children aged 12-15 years or 1200 mg/d in >15 years |
| Contraindications | Documented hypersensitivity; history of bone marrow depression; administration of MAOIs within last 14 d |
| Interactions | Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity especially if taken in first 4 wk of therapy; carbamazepine may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels) |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Do not use to relief minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks that require alertness |
Agents with effects in muscle contractions appear to be effective.
| Drug Name | Ketamine (Ketalar) |
|---|---|
| Description | Acts on the cortex and limbic system, decreasing muscle spasms. |
| Adult Dose | 0.4 mg/kg (one fifth of the usual anesthetic dose) IV; supplemental dose of 1/3 to 1/2 initial dose may be given for maintenance |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; angina; thyrotoxicosis; aneurysms; hypertension; congestive heart failure |
| Interactions | Ketamine increases CNS effects of narcotics, barbiturates, and hydroxyzine; thyroid hormones and muscle relaxants increase toxicity of ketamine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Resuscitative equipment should be immediately available during administration of medication |
| Drug Name | Lidocaine (Dilocaine, Xylocaine, Anestacon) |
|---|---|
| Description | Inhibits depolarization of type C sensory neurons by blocking sodium channels. |
| Adult Dose | 1 mg/kg IV loading dose followed by an infusion of 2 mg/min IV |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity to amide-type local anesthetics; avoid in Adams-Stokes syndrome and Wolff-Parkinson-White syndrome; avoid in severe sinoatrial, atrioventricular (AV), or intraventricular block, if artificial pacemaker not in place |
| Interactions | Coadministration with cimetidine or beta-blockers increases toxicity of lidocaine; coadministration with procainamide and tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Use a solution without preservatives; caution in heart failure, hepatic disease, hypoxia, hypovolemia or shock, respiratory depression, and bradycardia; may increase risk of adverse CNS and cardiac effects in elderly persons; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities |
These agents may reduce muscle contractions.
| Drug Name | Orphenadrine (Norflex) |
|---|---|
| Description | While exact mode of action not well understood, has shown clinical effectiveness in treating hiccups. |
| Adult Dose | 100 mg PO bid prn, 60 mg IM q12h prn |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; GI obstruction; glaucoma; myasthenia gravis; cardiospasm |
| Interactions | None reported |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in cardiac arrhythmias and congestive heart failure |
| Drug Name | Baclofen (Lioresal) |
|---|---|
| Description | May induce the hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level. Useful in patients for whom other agents are contraindicated (eg, those with renal impairment). |
| Adult Dose | 10 mg PO bid/qid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Opiate analgesics, benzodiazepines, alcohol, tricyclic antidepressants, guanabenz, MAOIs, clindamycin, and hypertensive agents may increase baclofen effects |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in patients with history of autonomic dysreflexia and when spasticity is utilized to obtain increased function; autonomic dysreflexia can result from withdrawal of this medication |
Agents with effects in spastic muscles have shown effectiveness.
| Drug Name | Morphine (Duramorph, Astramorph) |
|---|---|
| Description | DOC for analgesia due to reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained. |
| Adult Dose | 0.01-0.02 mg/kg IV q5-10min titrated to effect; 0.1-0.2 mg/kg IM q2-4h titrated to effect |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult |
| Interactions | Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate |
| Drug Name | Haloperidol (Haldol) |
|---|---|
| Description | Useful in treatment of irregular spasmodic movements of muscles. |
| Adult Dose | 2-5 mg PO q4-8h |
| Pediatric Dose | 0.05-0.15 mg/kg/d PO in 2-3 divided doses (not to exceed 0.15 mg/kg/d) |
| Contraindications | Documented hypersensitivity; narrow angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage |
| Interactions | May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects of haloperidol; haloperidol coadministration with anticholinergics may increase intraocular pressure; encephalopathylike syndrome associated with concurrent administration of lithium and haloperidol |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, watch for hypotension; caution in diagnosed CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue it occurs) |
| Drug Name | Chloral hydrate (Aquachloral, Supprettes) |
|---|---|
| Description | Has central nervous system depressant effects. Mechanism unknown. |
| Adult Dose | 500-1000 mg PO/PR; not to exceed 2 g/d |
| Pediatric Dose | 50-75 mg/kg PO/PR; not to exceed 2 g divided bid |
| Contraindications | Documented hypersensitivity; severe cardiac disease; hepatic or renal impairment; gastritis or ulcers |
| Interactions | May increase toxicity of warfarin, CNS depressants, alcohol, and furosemide |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in hyperbilirubinemia and porphyria |
A complex group of drugs that have central and peripheral anticholinergic effects as well as sedative effects. They block the active reuptake of norepinephrine and serotonin.
| Drug Name | Amitriptyline (Elavil) |
|---|---|
| Description | Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS. May also have analgesic effects. |
| Adult Dose | 10-40 mg PO qhs (50-150 mg may be necessary in some individuals) |
| Pediatric Dose | Children: 0.1 mg/kg PO hs; increase, as tolerated, over 2-3 wk to 0.5-2 mg/d hs Adolescents: 25-50 mg/d PO initially; increase gradually to 100 mg/d in divided doses |
| Contraindications | Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS |
| Interactions | Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly persons |
Mechanisms of action in the treatment of hiccups are not well understood.
| Drug Name | Ephedrine (Pretz-D) |
|---|---|
| Description | Stimulates release of epinephrine stores, producing alpha-adrenergic and beta-adrenergic effects. |
| Adult Dose | 25 mg IM q6h |
| Pediatric Dose | 3 mg/kg/d PO/SC |
| Contraindications | Documented hypersensitivity; angle-closure glaucoma; cardiac arrhythmias |
| Interactions | Theophylline, atropine, or MAOIs may increase toxicity; alpha-blockers and beta-blockers decrease vasopressor effects of ephedrine; cardiac glycosides and general anesthetics increase cardiac stimulation of ephedrine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in elderly persons and in those with diabetes mellitus, hyperthyroidism, hypertension, cardiovascular disease, prostatic hypertrophy, or cerebrovascular insufficiency |
| Drug Name | Methylphenidate (Ritalin) |
|---|---|
| Description | Stimulates cerebral cortex and subcortical structures. |
| Adult Dose | 5 mg PO qam or divided bid; not to exceed 60 mg/d |
| Pediatric Dose | 5 mg PO qam; optimal dose 0.3-0.7 mg/kg qd divided bid/tid |
| Contraindications | Documented hypersensitivity; glaucoma; Tourette syndrome; motor tics; patients with agitation, tension, and anxiety |
| Interactions | Reduces effects of guanethidine and bretylium; toxicity of phenytoin, tricyclic antidepressants, warfarin, primidone, and phenobarbital may increase when administered concurrently with methylphenidate; MAOIs increase toxicity of methylphenidate |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in dementia, seizures, and hypertension |
Brief episodes of hiccups are typically of little impact and often merely a source of amusement. In contrast, persistent and intractable can be of enormous impact, impairing all aspects of daily life. My thanks to those who have shared their stories including success or otherwise.
Article Last Updated: Aug 2, 2007
