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What causes Hyccups

What Causes Hyccups

Hiccups Aren’t Always Benign

Hiccups consist in intermittent spasmodic contractions of the diaphragm and accessory muscles of inspiration that causes the sudden closure of the glottis. [1] It’s something that all human beings experience, but doesn’t normally have any negative repercussions on health. On occasion though, hiccups can be so intense, frequent, and significant that it can prevent daily activities and in the most extreme cases, originate symptoms of severe malnutrition, insomnia, suicidal thoughts, and cause surgical wounds to open.

The frequency of spasms oscillates between 4 – 60 per minute in a relatively consistent fashion. [2] Unlike other reflexes, such as coughing or vomiting, hiccups do not serve any protective or physiological function. During pregnancy, detecting rhythmic movements attributed to hiccups in the fetus in the 3rd trimester by using an echography has led scientists to think that hiccupping represents a vestigial primitive reflex. Depending on its duration, hiccups can be classified as[3]:

  • Acute (also called transitory), which lasts less than 48 hours.
  • Persistent, lasts more than 48 hours.
  • Intractable, if it lasts more than 2 months.

Acute hiccups do not favor any gender. However, for unknown reasons, persistent and intractable types are more common in men. No differences have been found according to gender, race, or socioeconomic conditions otherwise. According to Dr. Stasia Rouse and Dr. Matthew Wodziak, of Loyola University Medical Center in Maywood, Ill, “Each year in the United States, about 4,000 people are hospitalized for hiccups. Men account for 91 percent of those with intractable hiccups, and most are over age 50.”[4] 

Figure – 1 Anatomy of the hiccups reflux arc (after Bailey 1943). Pathology affecting the brain, diaphragm, thoracic or abdominal viscera can stimulate vagal or phrenic afferents the activate the diffuse ‘hiccup center’ in the midbrain, brainstem and proximal cervical cord (Table 1). This triggers repetitive myoclonic contractions of the diaphragm and other respiratory muscles via the phrenic and the intercostal nerves (motor efferents colored red). Immediately afterwards activation of the recurrent laryngeal nerve (RLN) closes the glottis, producing the characteristic «hic» in hiccups.[6]
Figure – 1 Anatomy of the hiccups reflux arc (after Bailey 1943). Pathology affecting the brain, diaphragm, thoracic or abdominal viscera can stimulate vagal or phrenic afferents the activate the diffuse ‘hiccup center’ in the midbrain, brainstem and proximal cervical cord (Table 1). This triggers repetitive myoclonic contractions of the diaphragm and other respiratory muscles via the phrenic and the intercostal nerves (motor efferents colored red). Immediately afterwards activation of the recurrent laryngeal nerve (RLN) closes the glottis, producing the characteristic «hic» in hiccups.[6]

The contribution of the vagus and phrenic nerves explain the appearance of hiccups in processes that affect the digestive tract, thorax, and seems to be related to the presence of foreign bodies in the external auditory duct, which stimulate the auricular branch of the vagus nerve. 

     When people overeat, the stomach pouch tends to stretch out to accommodate food, and this can stimulate one of the primary hiccup nerves that trigger that phenomena. According to Timothy Pfanner, MD, assistant professor of medicine at the Texas A&M Health Science Center College of Medicine “Anything that causes your stomach to become distended can cause hiccups.” 7

    It has been proposed that there are pathways derived from the brain, cerebellum, and hypothalamus, which exert an inhibitory influence on the hiccup center, whose lesion would produce its appearance. There are locations of interest in the central nervous system called ‘centers of hiccups’ 8:

  • Spinal Cord between C3 and C5.
  • Medulla oblongata

Brain stem  

    In some studies, researchers have described the appearance of hiccups or hiccup-like manifestations when stimulating the peripheral zone of the reticular substance in the cerebral trunk of cats, proposing also that the action of gamma-aminobutyric-acid (GABA) is important in its control.9

     The efferent pathway is composed of the phrenic, vagus, accessory, recurrent laryngeal, intercoastal (T1 – T11) nerves, as well as nerve branches from C5 to C7. The effectors of the arch reflex are the hemidiaphragm with a predominance on the left side, trapezius muscles, and the glottis. 8

   The discharge of nerves responsible for hiccups has an approximate duration of 35 milliseconds. After diaphragmatic contraction has taken place, the glottis closes abruptly. The glottis is the space between the vocal cords, so essentially, what you hear from a hiccup is the involuntary clapping or shutting of our vocal cords.10

    It’s difficult to locate the place where the initial stimulus occurs, and once it does, it can travel through different pathways. In actuality, it’s thought that maybe the mechanism of closure of the glottis also acts not only on the laryngeal abductor and adductor muscles by way of their suppression and activation, respectively, but also on the intralaryngeal muscles. 11

The influence of partial pressure of carbon dioxide (PaCO2) in arterial blood on the frequency and amplitude of hiccups are well known. When PaCO2 goes down, the amplitude of hiccups goes up without modifying its frequency. On the other hand, when PaCO2 goes up, frequency goes down, but its amplitude is not altered. Frequency and amplitude seem to be controlled independently without evidence of correlation between the two. 12

Acute Hiccups

There are diverse causes of acute episodes, such as gastric overdistension after consuming copious amounts of food, the ingestion of sodas, sudden climate changes, food or drinks that are too hold or too cold, tobacco smoke, excessive alcohol consumption, and excessive emotional stress. 13

Eating too much or too quickly seems to depend on the stimulus of the vagus nerve, which results from overdistension or diaphragmatic irritation from a dilated stomach. “Hiccups usually occur when the stomach is full. Since the stomach is located under the diaphragm, if the full stomach rubs against the diaphragm it can get irritated, which will cause it to contract,” says  Dr. Rachel Reitan, the host of her own medical segment on News with a Twist, Dr. Rachel: The Teaching Doctor.14 In effect, there are mechanoreceptors located in the stomach capable of originating hiccups.

Persistent and Intractable Hiccups

A multitude of causes can originate these types of hiccups. In the majority of patients with hiccups, we can identify an organic etiology. The most frequent causes are cranial traumas, cerebrovascular accidents, encephalitis, neoplasms, alcohol, thoracic adenopathy, goiter, and gastroesophageal reflux disease (GERD). 15 This last one represents about half of the causal processes of this kind.  In some AIDS cases, this complication can be secondary to candidiasis or other esophageal condition.

Psychogenic causes associated with hiccups are anxiety, stress, and conversion disorder. In these cases, the psychological disorder can be a consequence, and not the cause, of chronic hiccups. 16 On rare occasions, there is no causal factor that can be discerned, so they are referred to as idiopathic hiccups.

Correlation between diseases responsible for hiccups and gender[17]
Figure 2 – Correlation between diseases responsible for hiccups and gender[17]

“Patients with intractable hiccups may experience issues including difficulty being able to eat or drink. There can be subsequent weight loss, the insomnia from having hiccups all night can be incredibly distressing, and then – not surprisingly – if you haven’t slept for two to three weeks, you can become depressed and anxious,” said Dr. Camielle Rizzo, an emergency room physician who’s also board-certified in hospice and palliative medicine at Middlesex Hospital in Middletown, Connecticut.[18]  All patients who seek medical counsel due to persistent hiccups should have basic laboratory tests requested. A few examples of these are complete blood count, formula, erythrocyte sedimentation rate, glucose, creatinine, calcium, and urea.

Other tests include a posteroanterior and lateral radiograph of the thorax and an electrocardiogram. The analytical data derived from these will help discard or suggest a toxic-metabolic etiology (diabetes, hypocalcemia, or hyponatremia), or a neoplastic one (increase of erythrocyte sedimentation rate, leukocyte alteration, etc.) The thoracic radiograph can orient the physician towards a mediastinal lesion, a hiatal hernia causing GERD or irritation of the phrenic and vagus nerves.

Finally, an electrocardiogram will allow the physician to discard pericarditis or ischemia. In the majority of cases, a clinical history, a meticulous physical exploration, and the set of data will be enough to provide a diagnosis to the patient. However, when the information above is not enough, the complementary help of specialists, such as a neurologist, pneumologist, gastroenterologist, and ENTs will most likely be required. They will handle the solicitation of tests they consider necessary, including an endoscopy, a pH-metry and esophageal manometry, a CAT scan, and magnetic resonance of the cranium and thoraco-abdominal cavities.

Sometimes, a patient that has a severe form of GERD can actually debut intractable type hiccups as a first symptom while coming out normal in an endoscopy and not have any symptom characteristic of GERD.[19]

Treatment

In popular lure, there are dozens of ways to cure a hiccup. Some make sense, others are preposterous. The easiest hiccup to cure is the acute type, which is what everyone normally experiences. Hippocrates postulated that coughing or sneezing does the trick, Plato suggests a few hits on the back, while other methods like breathing in a paper bag, flexing the knees towards the thorax, holding your breath as long as possible, and perform a Valsalva maneuver, among many others, have made their way into the mainstream.2 “You can hold your breath for 10 to 20 seconds, drink a glass of water without taking a breath, breathe into a paper bag for 20 to 30 seconds, jog in place or do jumping jacks for 30 seconds. Usually, one of those will do the trick,” said Dr.Andrea Paul, M.D.[20] 

The utility of most of these tips is relatively uncertain, and acute hiccups usually go away within a few minutes or hours on their own anyway.

With respect to persistent and intractable hiccups, an etiological treatment should be applied anytime it’s possible. For instance, GERD induced hiccups can be prescribed antisecretory drugs like omeprazole and if it does not go away, we can refer the patient to a surgeon for a possible Nissen fundoplication, or anti-reflux surgery.[21] 

In some cases, these patients have doubts on whether GERD is mainly responsible for the hiccups, which can be determined when all types of methods to eliminate GERD (medicinal and surgical included) fails to eliminate the hiccups.

An innumerable amount of medication has been utilized with the objective of getting rid of hiccups. In general, it could be said that we simply lack the rigorous studies necessary to know the mechanism of action of many cases. For the most part, patients need to try various medications to find the one that works for them.

Of all the drugs available, probably the most recommended is baclofen. It’s a derivative of GABA that inhibits presynaptic motor neurons and is used as an antispasmodic in some neurological diseases, such as multiple sclerosis and myelopathy. It’s mechanism of action seems to consist in inhibiting the nucleus of the hiccup. Very rarely, it can give rise to side effects like headaches, euphoria, ataxia, nausea, vomiting, and exacerbation of an existing psychosis. It’s administered orally and recommended to be taken in a progressive fashion. Dosage is 5-20 mg every 6 to 12 hours.

References:

  1. Fauzia Nausheen, et al., Neurotransmitters in Hiccups – Springerplus 2016) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988959/
  2. Cornelius J. Woelk, MD. Managing hiccups (Can Fam Physician. 2011 Jun) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114667/
  3. Kohse EK, et al. Chronic Hiccups: An Underestimated Problem (Anesth Analg. 2017 Oct) https://www.ncbi.nlm.nih.gov/pubmed/28759492
  4. Juan Brañuelas Quiroga, et al. Hiccups: a common problem with some unusual causes and cures (Br J Gen Pract. 2016 Nov) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072913/
  5. Daniel Howes. Hiccups: A new explanation for the mysterious reflex (Bioessays. 2012 Jun) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504071/
  6. Full-Young Chang, Ching-Liang Lu. Hiccup: Mystery, Nature and Treatment (J Neurogastroenterol Motil. 2012 Apr) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325297/
  7. Robert Preidt – Hiccups for a month? It can happen (HealthDay, August 2018)  https://www.webmd.com/digestive-disorders/news/20180803/hiccups-for-a-month-it-can-happen
  8. M. Steger, et al., Systemic Review: The Pathogenesis and Pharmacological Treatment of Hiccups. (Alimentary Pharmacology and Therapeutics, August 2015) https://onlinelibrary.wiley.com/doi/full/10.1111/apt.13374
  9. Hee-won Son, et al., “Stellate ganglion block for the treatment of intractable hiccups, a case report” , Korean Society of Anestheologists (Anesthesia Pain Medicine, April 2018)  http://www.anesthpainmed.org/journal/view.html?volume=13&number=2&spage=192
  1. Enzo Vettorato, et al., Hiccup-like response in a dog anesthetized with isoflurane (Case reports in veterinary medicine, June 2016) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005289/
  2. Christy Ludlow PhD, Laryngeal Reflexes: Physiology, Technique and Clinical Use (Journal of Clinial Neurophysiology, August 2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527097/
  3. [Online] MayoClinic Staff, Hiccups>Overview (May 2017) https://www.mayoclinic.org/diseases-conditions/hiccups/symptoms-causes/syc-20352613
  4. Rachel Reitan, What causes hiccups and how do I get rid of them? (Video June 2016) https://wgno.com/2016/06/24/dr-rachel-hiccups/
  5. Michael O. Schroeder , What to do about hiccups that won’t quit  [Online] HealthUsNews https://health.usnews.com/health-care/patient-advice/articles/2018-09-11/what-to-do-about-hiccups-that-wont-quit
  6. Douglas C Barnhart, Gastroesophageal reflux disease in children. (PubMed, August 016) https://www.science.gov/topicpages/g/gastroesophageal+reflux+disease.html
  7. Texas A&M University. “What are my hiccups telling me?.” ScienceDaily, 11 February 2016.sciencedaily.com/releases/2016/02/160211192345.htm
  8. JMS Pearce, A Note on Hiccups (Journal of Neurology, Neurosurgery, and Psychiatry, Volume 74, issue 8, 2003) https://jnnp.bmj.com/content/74/8/1070
  9. O Eroglu, The effect of gender differences in protracted hiccups. (Nigerian Journal of Clinical Practice, October 2018)  http://www.njcponline.com/article.asp?issn=1119-3077;year=2018;volume=21;issue=10;spage=1356;epage=1360;aulast=Eroglu
  10. Daphne Ang, Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy (Singapore Medical Journal, October 2016)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075954/
  11. [Online] Foxnews, Everything you ever wanted to know about hiccups and how to get rid of them (Digestive Health, October 2015) https://www.foxnews.com/health/everything-youve-ever-wanted-to-know-about-hiccups-and-how-to-get-rid-of-them
  12. Douglas C Barnhart, Gastroesophageal reflux disease in children. (PubMed, August 016) https://www.science.gov/topicpages/g/gastroesophageal+reflux+disease.html
Robert Velasquez
27 July, 2019

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Hello everyone, my name is Robert Velazquez. I am a content marketer currently focused on the medical supply industry. I studied Medicine for 5 years. I have interacted with many patients and learned a lot...read more:

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