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You are watching: Singultus is the medical term for what

StatPearls . Treasure Island (FL): StatPearls Publishing; 2021 Jan-.


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Continuing education Activity

Hiccups can be acute, lasting much less than 48 hours, persistent, lasting end 2 days, or intractable, lasting an ext than one month. They can result from a variety of causes. In particular, hiccups are frequently caused through gastrointestinal obstacle such as gastroesophageal reflux. Other causes include medication side-effects, cardiovascular disorders, central nervous device disorders, ear, nose, and throat disorders, psychogenic disorders, or metabolic disorders. Ths task reviews the spectrum the hiccups from acute come intractable, outlines the causes, and offers references for medical treatment based upon clinical presentation. This task stresses the function of the interprofessional team in the treatment of influenced patients.

Objectives:
Outline medications and also medical conditions known to cause hiccups.
Describe beneficial bedside maneuvers because that aborting acute hiccups.
Identify medical therapies because that aborting persistent or intractable hiccups.
Explain a well-coordinated interprofessional team strategy to administer effective care to patients impacted by persistent or intractable hiccups.
Access totally free multiple an option questions on this topic.


Introduction

Hiccups are a no uncommon incident that most people experience at some point in their lifetime. The clinical term is singultus, which derives from the Latin “singult” meaning ‘to catch one’s breath if sobbing.’  Hiccups result from a sudden and involuntary convulsion of the diaphragm and also intercostal muscles. One abrupt closure that the glottis complies with the contractions i m sorry produces the characteristics “hic” sound. Often, these episodes are transient and resolve in ~ 48 hours. Castle can occur in adults, children, infants, and also in utero. In adults, they offer no physiological purpose. The id is that they may play a duty in respiratory muscle maintain in utero.<1>  Acute hiccups can be uncomfortable, and a brief annoyance, but persistent and intractable hiccups have actually a far-reaching impact on top quality of life through interfering through eating, sleeping, speaking, and also social activities, and can it is in a harbinger that serious clinical pathology.<2>


Etiology

The group of hiccups is by your duration. Acute hiccups room of less than 48 hours duration, persistent last end 2 days, and also intractable last over a month. Together acute hiccups space self-limited and usually unreported, many of the research has concentrated on persistent and intractable hiccups. There space various causes of hiccups including organic causes, psychogenic, idiopathic, or medication-induced. Persistent and intractable hiccups may represent a an ext serious underlying etiology.

Gastrointestinal processes, an especially gastroesophageal reflux condition (GERD) and also associated hiatal hernias, are implicated as the many common cause of acute hiccups.<3><4>  The incidence of hiccups in GERD patients has been reported together high together 10%.<5>  Distension of the stomach by big meals or carbonated beverages or irritation from spicy foodstuffs or alcohol are usual associations. In patients v esophageal tumors, as plenty of as one in four can existing with persistent hiccups.<6>  Similarly, overexcitement or anxiety, particularly if add by end breathing or waiting swallowing (such as with laughing fits), can trigger the hiccups reflex. <7>

Many drugs correlate through hiccups, specifically alcohol. Part drugs, such together benzodiazepines, have a dose-dependent and an inverse relationship with hiccups. At low doses, benzodiazepines correlate through the breakthrough of hiccups. At higher doses, they may be valuable in the therapy of hiccups. Chemotherapeutic agents and some glucocorticoids have presented a strong association with hiccups. Almost 42% that patients taking both cisplatin and also dexamethasone develop hiccups.<8><9> other medications associated with hiccups encompass various chemotherapeutic agents, alpha-methyldopa and also inhaled anesthetics.

Numerous reports exist the persistent and intractable hiccups because of a multitude the etiologies, including:


Cardiovascular disorders: atrial pacing, aortic aneurysm (thoracic or abdominal), catheter ablation of atrial fibrillation, myocardial infarction, pericarditis, temporal arteritis
Drugs: alpha-methyldopa, aripiprazole, azithromycin, benzodiazepines (diazepam, midazolam), chemotherapeutics (carboplatin, cisplatin, etoposide, fluorouracil, irinotecan, levofolinate, oxaliplatin), dexamethasone, donepezil, ethanol, levodopa, methohexital, morphine, pergolide, piribedil, sulfonamides, tramadol
ENT disorders: a cough, foreign body irritation of tympanic membrane (e.g., hair), goiter, laryngitis, neck cyst, neoplasms, pharyngitis, current intubation
Infectious disorders: Helicobacter pylori, herpes simplex, herpes zoster, influenza, malaria, neurosyphilis, tuberculosis
Intrathoracic disorders: asthma, bronchitis, diaphragmatic tumor or a hernia, empyema, lymphadenopathy, mediastinitis, neoplasms, pleuritis, pneumonia, pulmonary embolus
Metabolic/endocrine disorders: hypocapnia, hypocalcemia, hypokalemia, hyponatremia, diabetes mellitus, uremia

Epidemiology

Hiccups take place in all ages, from in utero to the elderly.  The incidence and prevalence of hiccups in the community are unknown, and also there does not show up to be differences based upon racial or geographical variation.  Reports indicate there space as plenty of as 4,000 admissions yearly in the U.S. Because that hiccups.<20>  Intractable hiccups have a predominance because that older males, v an odds ratio of 2.4, and also those with higher height and weight.<5><21><22><23> The incidence the persistent hiccups is greater in patients with certain disorders, especially those with main nervous device disorders such as Parkinson’s Disease, advanced cancer where the incidence might be together high as 4-9%, and also 8-10% in those v gastroesophageal reflux disease (GERD).<7><5><24><25>


Pathophysiology

Hiccups are believed to be because of a complicated reflex arc written of three main units. Any kind of condition that acts on one of these pathways has actually the potential come induce hiccupping. 

First, the afferent limb is composed that the vagus nerve, the phrenic nerve, and the peripheral sympathetic nerves providing the viscera. Second, the main processing unit likely entails the interaction in between various midbrain and also brainstem structures, such as the medulla oblongata and also reticular formation, chemoreceptors in the periaqueductal gray, glossopharyngeal and also phrenic nerve nuclei, solitary and also ambiguous nuclei, hypothalamus, temporal lobes and also upper spinal cord at level C3 come 5.<9><20>  central neurotransmitters affiliated in this reflex encompass dopamine, gamma-aminobutyric mountain (GABA) and also serotonin.<20><26>  Third, the efferent portion of the reflex is composed of the phrenic nerve supplying the diaphragm and the accessory nerves giving the intercostal muscles.<20> 

Hiccups frequently repeat in ~ cycles of 4 come 60 every minute, depending on the individual. The diaphragmatic spasm is regularly unilateral, and also the left hemidiaphragm is involved an ext than the right.<2>  after ~ diaphragmatic spasm, the reflex is perfect by activation of the recurrent laryngeal nerve resulting in closure the the glottis. There is no closure of the glottis, hyperventilation would certainly occur.<20>  Hiccups are inhibited by elevations in partial push of carbon dioxide (PCO2), vagal maneuvers, GABA-ergic agents (such together baclofen, gabapentin) and also dopamine antagonists (such as chlorpromazine, haloperidol, metoclopramide) or agonists (amantadine).<26>  Hiccups become persistent together a form of diaphragmatic myoclonus as result of excess task of the solitary cell core of the medulla.<27><28>


History and also Physical

Evaluating a patient v hiccups warrants a thorough medical history review. Ask around precipitating causes, such as large meals, excited or emotionally stress.  Inquire concerning associated symptom such together gastroesophageal reflux, coughing, weight loss, and ab pain. Ask around neurologic symptoms that could suggest a medullary stroke, many sclerosis or Parkinson"s disease.  Hiccups during sleep are uncommon and also can occur with gastroesophageal, neurologic or pulmonary disorders, however negate psychogenic cause.  Ask about recent surgery, known cancer or chemotherapy.  A comprehensive medication review may identify a most likely cause, and if discontinuing this offending medicine provides significant relief then origin is confirmed. 

In cases of persistent and also intractable hiccups, one should investigate essential causes. A complete HEENT evaluation may reveal processes such together a hair or international body pressing versus the tympanic membrane, masses, goiters, tonsillitis, and pharyngitis.  listen to the lung sound to assess for thoracic reasons such as pneumonia or empyema.  Palpate the abdomen for tenderness or mass to exclude obstruction, volvulus, pancreatitis, hepatitis or mass.  A complete neurological exam may expose CNS pathology such as strokes and also tumors, though it is rarely for hiccups to it is in the only presenting symptom.


Evaluation

Acute hiccups are frequently benign and usually execute not require a workup, yet persistent and intractable hiccups should cause a thorough evaluation to recognize a treatable cause.  that is reasonable to obtain lab work for review of electrolyte abnormalities or to dominance out infectious and neoplastic procedures not determined on history and physics exam.  Laboratory research studies such together electrolytes, calcium, blood urea nitrogen (BUN), creatinine, lipase, and liver tests can be useful.  A chest radiograph may recognize intrathoracic sources of hiccups such together pneumonia, empyema, diaphragmatic hernia, adenopathy or aortic disease.<29> 

The guiding of further imaging or interventions is finest by the duration of hiccups, history and physical test findings.  because that persistent or intractable hiccups connected with neurologic symptom or signs, brain imaging through computerized tomography (CT) or magnetic resonance imaging (MRI) may demonstrate reasons such as stroke, lot of sclerosis, tumor, syringomyelia, neuromyelitis optica, aneurysm or vascular malformation.<30> In rare cases, cerebrospinal fluid is essential to to exclude, meningitis or encephalitis. For some cases, thoracic or abdominal CT imaging may recognize cancer, aneurysm, abscess or a hernia.  Referral to gastroenterology for upper endoscopy is vital to exclude, lesions (such together esophageal cancer) in those situations of persistent hiccups refractory to initial antacid and proton pump inhibitor therapy.

It is important to review blood gases in any type of ventilated patient that develops hiccups. Hiccups in ventilated patients may reason ventilator desynchronization, serious respiratory derangements, and hemodynamic changes.<31>  


Treatment / Management

In the acute phase, hiccups are likely to be terminated by a selection of straightforward physical maneuvers supported by anecdotal evidence. Most of the maneuvers aim for some part of the hiccup reflex arc.  The frequency the hiccups decrease together PCO2 rises,<32> so Valsalva, breath holding, and breathing right into a paper bag may be therapeutic.  Supra-supramaximal incentive is a method where subject exhales completely, climate inhale deeply and hold for 10 seconds, then without exhaling inhale two times again, each time holding for 5 seconds.<33>  various other techniques include stimulation that the vagus nerve with the nose, ear, and throat by utilizing cold drinks, pulling on the tongue,<34> press on the carotid, eyeballs or in both exterior auditory canals, sipping vinegar, swallowing sugar, stimulating the uvula or posterior nasopharynx (with smelling salts or sleep vinegar), Valsalva maneuver, and gargling, gagging or even self-induced vomiting.<7><35> much more bizarre techniques reported have had sexual stimulation and digital rectal massage.<36><37> There room reports of suboccipital release and also osteopathic/chiropractic manipulation techniques.<38><39>  every one of these techniques show up to it is in much much more effective in the acute phase. The persistent step is normally multifactorial and also more complicated to treat. 

 Important measures in the treatment of persistent and intractable hiccups are, first, to evaluate whether the patience is utilizing a medication recognized to induce hiccups, and second, to recognize whether hiccups are associated with GERD. Discontinuation of an offending medication or usage of an different agent (such as methylprednisolone instead of dexamethasone) have the right to resolve medication-induced hiccups.<40>  v as many as 80% of persistent hiccup cases related to GERD,<41><3> an initial therapeutic psychological of antacids, antihistamines (such together famotidine) or proton pump inhibitor (such together omeprazole) might be successful,<42><41> and this technique has been suggested as first-line therapy.<7>  

In the persistent phase, most studies have evaluated pharmacotherapies acting on one or much more components of the reflex arc. Pharmacotherapy is aimed at neurotransmitters and can be broken down into main and peripheral treatments though some act on both. The neurotransmitters affiliated in central processing include GABA, dopamine, and also serotonin. Peripherally, they include acetylcholine, histamine, epinephrine, and norepinephrine. Classically, chlorpromazine had been the drug of selection for persistent hiccups and also remains the just drug for hiccups approved by the U.S. Food and Drug management (FDA). Chlorpromazine acts together an antagonist ~ above multiple main and peripheral neurotransmitter sites consisting of dopamine, serotonin, histamine receptors, alpha-adrenergic receptors, and muscarinic receptors.<20> Due come the multiple web page of action, the drug might have far-ranging side results for some patients. Other common antipsychotics, such together haloperidol or risperidone, have been tried through varying levels of success. Often, the side impacts of the common antipsychotic drugs may be unbearable because that the patient.

The most commonly studied drugs for persistent or intractable hiccups room metoclopramide and also the GABA agonists baclofen and also gabapentin.<26> compared to the usual antipsychotics, these 3 drugs have actually a far better side result profile. If no etiology is found with a thorough exam, metoclopramide, gabapentin or baclofen are reasonable second-line therapies. Metoclopramide acts centrally as a dopamine antagonist and peripherally by increasing gastric motility and also has prospered in relief of hiccups from cancer, punch and mind tumors.<7><43>  Baclofen acts to decrease neuroexcitation and also induce muscle relaxation and also has been efficient for intractable hiccups in stroke patients and also idiopathic reasons without gastroesophageal disease.<44><45><46> Similarly, gabapentin, structurally comparable to GABA, reduce neuroexcitation through binding voltage-gated calcium channels and also decreasing the release of excitatory neurotransmitters. In one case series, gabapentin has been report to it is in 66 to 88% efficient in cancer and also brainstem hit patients.<9><24><27>

There space a range of medications argued for the therapy of persistent hiccups in anecdotal reports such together amantadine,<47> amitriptyline, antipsychotic agents (haloperidol, risperidone, olanzapine),<9> atropine, benzonatate, carvedilol, glucagon, ketamine, midazolam, nifedipine, nimodipine, orphenadrine, and also valproic acid.<26> therapy for intraoperative hiccups has actually been with various intravenous medications consisting of atropine, ephedrine, dexmedetomidine, ketamine, and lidocaine.<48>  numerous other shipment methods have discovered use with regional anesthetic including oral viscous lidocaine,<49> lidocaine gelatin in the exterior auditory canal,<50> and also subcutaneous infusions.<51>

For instances refractory to medical therapy, much more invasive methods for management incorporate acupuncture, hopeful pressure ventilation, vagus nerve stimulators,<52>and stellate or phrenic nerve block.<53><54> tiny trials assistance acupuncture through promising outcomes for intractable hiccups in the setup of cancer and also stroke.<55><56><57> offered the reasonably low complication rate with a potential benefit, it might be a reasonable alternate for part patients who space too sick or yonsi to experience pharmacotherapy or an ext invasive techniques.

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<58>  Positive pressure ventilation through elective intubation has displayed to occupational in some case reports.<59> If considering cut or blocking the phrenic nerve for symptomatic relief, the is vital to ensure both hemi-diaphragms are functional prior to the procedure.