Materiały źródłowe

• #1 Hiccup: Mystery, Nature and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3325297/

  Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. […] A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. […] The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. […] In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. […] The pathophysiological mechanism of hiccup is related to lesions in its reflex arc shown in Figure. […] The hiccup reflex arc consists of 3 components, the afferent limb including phrenic, vagus and sympathetic nerves to convey somatic and visceral sensory signals, the central processing unit in the midbrain and the efferent limb traveling in motor fibers of phrenic nerves to diaphragm and accessory nerves to the intercostal muscles, respectively.

• #1 Hiccups: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/775746-overview

  Hiccups appear to serve no purpose in humans or other mammals. Often, only a single hemidiaphragm is affected. The left hemidiaphragm is affected in 80% of cases, though bilateral involvement may occur. […] Despite centuries of contemplation, the exact pathogenesis of hiccups remains a mystery. Hippocrates and Celsus associated hiccups with liver inflammation and other conditions. Galen believed that 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: Afferent limb: Phrenic and vagus nerves and sympathetic chain arising from T6 to T12; Hiccup center: Nonspecific location between C3 and C5; Connections to the respiratory center, phrenic nerve nuclei, medullary reticular formation, and hypothalamus; Efferents: Phrenic nerve (C3-5), anterior scalene muscles (C5-7), external intercostals (T1-11), glottis (recurrent laryngeal component of vagus), inhibitory autonomic processes, decreasing esophageal contraction tone, and lower esophageal sphincter tone.

• #1 Hiccup: Mystery, Nature and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3325297/

  Accordingly, any physical and chemicals irritants and inflammatory and neoplastic conditions involving the hiccup reflex may cause hiccup. […] Unfortunately, owing to the long trajectory of afferent and efferent nerves and the diffuse central processes involving the hiccup reflex arc, the accurate diagnosis of lesions in the arc and trying to terminate the pathological processes in the intractable events are often very difficult. […] Among the neurotransmitters involved in the process of hiccup, both dopamine (D) and gamma-aminobutyric acid (GABA) have been documented. […] In the review of recent literature, too many causes of hiccups have been reported. […] According to the sites of lesion, hiccup may originate either from central or peripheral pathways. […] Brain ischemia or stroke is not rare among the individuals with intractable hiccup and in some patients cerebrovascular cause was correctly diagnosed months later.

• #1 Neurotransmitters in hiccups | SpringerPlus | Full Text

  https://springerplus.springeropen.com/articles/10.1186/s40064-016-3034-3

  The central component for hiccups lies in the medulla and is thought to be entirely separate from the pathways involved in rhythmic breathing. […] Dopamine, gamma-amino-butyric-acid (GABA), serotonin, glutamate, and glycine neurotransmitters can regulate this central mechanism. […] The mechanism of action of hiccups might be mediated through agonizing 5-HT1A and antagonizing 5-HT2A receptors to enhance the activity of the phrenic nerve, thereby inducing hiccups. […] It is postulated in a study that the GABA-containing cells in the nucleus raphe are the source of GABA-nergic inhibition of the hiccup center. […] The reflex arc is potentially mediated by central neurotransmitters (GABA, dopamine, and serotonin) and peripheral neurotransmitters (epinephrine, norepinephrine, acetylcholine, and histamine). […] Further research is needed to characterize the neurotransmitters involved in hiccups for potential new therapeutic targets.

• #1 :: Journal of Neurocritical Care

  https://www.e-jnc.org/m/journal/view.php?doi=10.18700/jnc.200018

  The efferent response of the reflex is carried by the phrenic nerve to the diaphragm. […] Various neurotransmitter pathways of the brainstem and medulla, including those involving dopamine, serotonin, opioids, calcium channels, and GABA are possibly involved in mediating hiccups. […] Any process that affects the peripheral afferent, central, or efferent components of the proposed reflex arc can trigger hiccups. […] Central hiccups could occur with any lesions along the pathway from the CNS to the phrenic nerve, especially with lesions of the brain stem, such as tumors and ischemic stroke. […] Chronic hiccups have been reported following hemorrhagic and ischemic strokes, cerebellar aneurysms, and neuromyelitis optica. […] The dorsal area of the medulla is commonly associated with hiccups as it incorporates a number of complex structures which conciliate the reflex arc, including the vagus nerve, respiratory center, solitary nucleus, nucleus ambiguus, central sympathetic tract, and spinal tract of trigeminal nucleus.

• #1 Hiccup: Mystery, Nature and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3325297/

  There is no doubt that any space occupying lesion in the brain has the chance to elicit hiccup. […] A patient with mediastinal lymph node sarcoidosis, which was likely the lesion invading the hiccup reflex arc, had persistent hiccup that did not respond to steroid therapy. […] Hiccup has been an unrecognized symptom of esophageal cancer. […] It is well known that GERD is commonly associated with belching. […] Post-operative hiccups were reported in subjects receiving various surgeries, for example, Whipple operation and colectomy. […] Serious hiccup is not unusual among the cancer patients. […] Twenty percent of parkinsonism (PD) patients had frequent hiccups compared to 3% of the controls. […] Interestingly, many measures on human body have been known to elicit serious hiccups.

• #1 Hiccups as a myocardial ischemia symptom – Polish Archives of Internal Medicine

  https://www.mp.pl/paim/issue/article/338

  A hiccup is involuntary, paroxysmal inspiratory movements of the chest wall associated with diaphragm and accessory respiratory muscle contractions, with the synchronized closure of glottis. The mechanism underlying this common primitive reflex plays an important role in protecting airways against esophageal aspiration. […] The hiccup reflex mechanism is based on the afferent pathway (vagus and phrenic nerve and sympathetic fibers innervating chest organs, the abdomen, the ear, the nose and the throat stimulation, and the stimulation of hiccup center in the central nervous system, mainly reflecting psychogenic or metabolic disorders) and the efferent pathway (phrenic nerves). […] The most common causes of pathologic symptomatic hiccups are nervous system diseases, either the central nervous system (proliferative, angiogenic, inflammatory disorders), or the peripheral nervous system: the irritation of the phrenic nerve (proliferative disorders, goitre) and the vagus nerve (otolaryngologic diseases, meningitis, esophageal, stomach and duodenal diseases, hepatitis, pancreatitis, enteritis). The vagus nerve irritation with subsequent hiccups may be caused by chest disorders (injury, surgery) and heart diseases (myocardial infarction). In the present paper we describe the case of a 62-year-old male with recurrent hiccups associated with exertion as a secondary symptom of myocardial ischemia.

• #1 Hiccups, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17672-hiccups

  Some medications can also cause persistent hiccups. Examples include: Dopamine agonists. Benzodiazepines (at low doses). Some chemotherapy drugs. Dexamethasone. Azithromycin. […] Persistent hiccups may also happen after certain surgeries or procedures, including those that require general anesthesia.

• #1 Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172057

  Our investigation on dexamethasone administration routes and hiccups revealed a relationship between the intravenous route and induction of hiccups. […] Therefore, dexamethasone use alone appears to induce hiccups. This result suggests that dexamethasone is an important drug associated with the induction of hiccups.

• #1 Hiccup – Wikipedia

  https://en.wikipedia.org/wiki/Hiccup

  A leading hypothesis is that hiccups evolved to facilitate greater milk consumption in young mammals. The coordination of breathing and swallowing during suckling is a complicated process. Some air inevitably enters the stomach, occupying space that could otherwise be optimally used for calorie-rich milk. […] An international respiratory research group composed of members from Canada, France, and Japan proposed that the hiccup is an evolutionary remnant of earlier amphibian respiration. Amphibians such as tadpoles gulp air and water across their gills via a rather simple motor reflex akin to mammalian hiccuping. The motor pathways that enable hiccuping form early during fetal development, before the motor pathways that enable normal lung ventilation form. Thus, the hiccup is evolutionarily antecedent to modern lung respiration. […] The phylogenetic hypothesis may explain hiccups as an evolutionary remnant, held over from our amphibious ancestors.

• #1 What causes hiccups and how can you get rid of them?

  https://theconversation.com/what-causes-hiccups-and-how-can-you-get-rid-of-them-196557

  Hiccups are caused by a reflex arc: a neuromotor pathway that translates a sensation into a physical response. […] The sensation signals travel to a part of the brain which, along with the top of the spinal cord, is known as the hiccup centre. […] From the hiccup centre, the signals travel back out to the diaphragm and the muscles that lay between your ribs (intercostal muscles), causing them to twitch. […] Anything that affects the arc can lead to hiccups. […] Hiccups have even been observed in healthy fetuses during prenatal ultrasound checks. […] In fact, some researchers believe hiccups are a mechanism to help prepare the lungs for breathing shortly after birth. […] Persistent and intractable hiccups, known collectively as chronic hiccups, can be quite distressing and may signify a serious underlying cause, so it’s important to see your doctor.

• #1 :: Journal of Neurocritical Care

  https://www.e-jnc.org/m/journal/view.php?doi=10.18700/jnc.200018

  Persistent hiccups have the capacity to induce major disabling impact on general health and cause exhaustion, sleep deprivation, malnutrition, dehydration, depression, wound dehiscence, and even death in extreme cases. […] The occurrence of hiccups in a patient receiving mechanical ventilation causes desynchronization and possible respiratory alkalosis leading to lung damage and hemodynamic alterations. […] Persistent and IH are a risk factor for ventilator-associated pneumonia in intubated patients.

• #1 Hiccups | Canadian Cancer Society

  https://cancer.ca/en/treatments/side-effects/hiccups

  Hiccups are unintended spasms of the diaphragm followed by quick closing of the vocal cords. The exact cause of hiccups is not known. Hiccups may be caused by irritation of the nerves that control the muscles used for breathing, including the diaphragm. […] People with advanced cancer have a higher than average chance of getting persistent or intractable hiccups. Up to about 10% of people with advanced cancer get these long-lasting hiccups. […] Persistent and intractable hiccups can be difficult to treat. Your healthcare team may suggest the following ways to treat these hiccups. Your doctor may prescribe medicines, such as: […] To treat intractable hiccups, doctors may block or disrupt the signals in the nerves that control the diaphragm (called the phrenic nerves). […] Sometimes doctors may stimulate the nerves by using electrical signals. They may stimulate the vagus nerve, which helps control the diaphragm, and maybe the phrenic nerves too. […] If other treatments fail, the doctor may cut the phrenic nerves (called a phrenicotomy) to permanently stop the nerve signals to the diaphragm, but even this does not cure all cases of intractable hiccups.

• #1 Analysis of Factors Associated with Hiccups Using the FAERS Database

  https://www.mdpi.com/1424-8247/15/1/27

  In this study, we used the large number of cases in the FDA adverse-event reporting system (FAERS) database to investigate risk factors for drug-induced hiccups and to explore the relationship between hiccups and gender. […] The multivariate analysis showed nicotine products to be key suspect drugs for both men and women. […] This study can contribute to elucidating the mechanism underlying this phenomenon. […] Although the exact mechanisms of the central link of the hiccup reflex arc are not clear, in their review, Nausheen et al. reported that the hiccup reflex arc is potentially mediated by central neurotransmitters (γ-aminobutyric acid (GABA), dopamine, and serotonin) and peripheral neurotransmitters (epinephrine, norepinephrine, acetylcholine, and histamine). […] The results of the multivariate analysis showed that, as in previous reports, male gender was extracted as an independent risk factor for hiccups.

• #1 Demographic and Clinical Risk Factors of Hiccups

  https://www.gavinpublishers.com/article/view/demographic-and-clinical-risk-factors-of-hiccups

  Hiccups are caused mainly by diaphragmatic myoclonus, a brief involuntary twitching of the diaphragmatic muscles, together with coordinated contraction of the glottic closure group of muscles. […] While the clinical features and pathogenesis of hiccups have been partially elucidated, there has been no complete physical examination of the associations between hiccups and clinical variables such as primary disease. […] We suggest that low BMI is a reliable physical index related to hiccup risk, while chemotherapy and certain malignant tumors are clinical risk factors. These results may assist in elucidating the underlying mechanisms and guiding therapy to reduce hiccup risk. […] We report for the first time that BMI is an independent risk factor for hiccups in patients above 40 years old. We also confirmed that chemotherapy, certain malignant tumors, and neurovascular diseases are risk factors. These results may enable the identification of high-risk patients and treatment regimens, thereby reducing risk and improving quality of life. Moreover, such information may help clarify the pathomechanisms of hiccups.

• #1 Intraoperative Laryngeal Mask Airway-Related Hiccup: An Overview

  http://www.transpopmed.org/articles/tppm/tppm-2019-7-103.php

  Vagus nerve innervates the pharynx and upper esophagus and it is postulated that stimulation of the vagus nerve while insertion or rapid inflation of the laryngeal mask airway acts as a trigger for initiating hiccups. […] The pathophysiology of gastroesophageal reflux in most patients with GERD revolves around transient or lasting LES relaxation. […] Considering the pressure difference across LES is responsible for reflux after hiccup, it is also likely that patients with GERD might be at increased risk of developing hiccup. […] The incidence of laryngeal mask airway -related hiccup is estimated to be around 5%. […] Different models of laryngeal mask airway may have different impact on the incidence of laryngeal mask airway -related hiccup. […] The external larynx lift technique was found to be potentially less likely to cause tissue trauma of the upper airway during laryngeal mask airway insertion.

• #1 What causes hiccups and how can you get rid of them?

  https://theconversation.com/what-causes-hiccups-and-how-can-you-get-rid-of-them-196557

  One study from France found 80% of patients with chronic hiccups had abnormalities in their oesophagus and stomach, with reflux disease being the most common finding. […] After a thorough investigation, the underlying cause should be treated, where possible. […] Other medications with a strong evidence base that are used to treat hiccups include the anti-nausea drug metoclopramide and baclofen, which is used to treat muscle spasticity (excessive tightness or tone). […] FISST is thought to stop the hiccup reflex arc by stimulating the sensory nerves to cause contraction of the diaphragm and glottis.

• #1 Hiccups as the first presentation of secondary adrenal insufficiency associated with advanced cervical cancer in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2022 Issue 1 (2022)

  https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM22-0286.xml

  Hiccups are a common symptom characterized by intermittent spasmodic contraction of the diaphragm. […] Patients with intractable hiccups often have abnormalities of the diaphragm, medulla oblongata, and lesions affecting nerve fibers connecting them. […] Adrenal insufficiency (AI) is one of the causes of hyponatremia. […] Hiccups could be the first manifestation of adrenal insufficiency (AI). […] Hiccups in patients with AI are often mediated by hyponatremia. […] The differential diagnosis should include AI-induced hyponatremia if hiccups occur in patients with advanced cancer, as metastasis to adrenal gland or pituitary gland could cause AI. […] To our knowledge, this is the first case of a patient presenting with hiccups as the first symptom of secondary AI. […] AI is characterized by cortisol deficiency and can be classified as primary AI and secondary AI.

• #1 Prolonged hiccups induced by renal infarction: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-024-04347-z

  Hiccups can be induced by various clinical conditions. […] It is hypothesized that the inflammation of the right kidney infarction stimulated the diaphragm and induced prolonged hiccups in this patient; this theory is supported by the computed tomography images. […] Hiccups due to renal infarction are rare. […] It was hypothesized that the inflammation of the right kidney infarction stimulated the diaphragm and induced prolonged hiccups in this patient, based on the CT images. […] These findings were interpreted as inflammation due to an infarction in the right kidney, affecting the diaphragm and inducing hiccups because of the proximity between the kidney and the diaphragm. […] Therefore, renal disease should be considered in patients with prolonged hiccups. […] Determining the mechanism between renal infarction and hiccups is an interesting topic for further research.

• #1 Intraoperative Laryngeal Mask Airway-Related Hiccup: An Overview

  http://www.transpopmed.org/articles/tppm/tppm-2019-7-103.php

  Hiccup is an involuntary contraction of the diaphragm and intercostal muscles resulting in sudden inspiration and closure of the glottis. […] Hiccup can lead to have increased aspiration risk. Hiccup are is an incompletely understood phenomenon with multiple etiologies. […] Intraoperative hiccup related to laryngeal mask airway placement has been reported, and it presents unique challenges in diagnosis and management. […] Hiccup is believed to involve a reflex arc. The afferent limb consists of vagal, phrenic and sympathetic chain from T6-12. […] The hiccup center is located at the posterolateral part of the medulla oblongata of the brain stem. […] Stimulation anywhere along the afferent pathways may potentially lead to hiccups. […] The distal end of a well seated laryngeal mask airway lies over the proximal esophagus, and sudden and rapid stretch of mechanoreceptors in the proximal esophagus is known to trigger the hiccup reflex.

• #1 Demystifying the Relationship Between Alcohol and Hiccups – Alis Behavioral Health

  https://www.alisbh.com/blog/hiccups-when-drunk/

  Hiccups can be an unwelcome side effect of consuming alcohol, leaving many people wondering about the relationship between the two. In this section, we will explore the mechanism of alcohol-induced hiccups and the factors that contribute to the hiccup reflex. […] Alcohol can trigger hiccups by causing various effects on the body. One of the main reasons is that alcohol has the potential to distend the stomach, irritate the digestive system, and increase acid production, which can lead to acid reflux and subsequently trigger hiccups. The irritation or stimulation to the vagus and phrenic nerves, which are involved in the hiccup reflex, can also be prompted by alcohol consumption. […] When the stomach becomes distended or irritated, it can press on or irritate the diaphragm, the muscle responsible for breathing. This irritation can cause the diaphragm to contract involuntarily, resulting in hiccups. Additionally, alcohol’s effect on the digestive system and esophagus can contribute to the hiccup reflex.

• #1 Why do chili peppers give us the hiccups?

  https://www.medicalnewstoday.com/articles/318238

  Chili peppers contain a chemical compound called capsaicin, which is part of a group of chemicals that give chilies their individual taste and heat profile. Capsaicin can activate neurons in the diaphragm, which contracts and causes hiccups. […] Hiccups are thought to be caused by an involuntary contraction, or spasm, of the diaphragm, followed by contraction of the glottis. Airflow into the windpipe becomes temporarily blocked. When incoming air strikes the glottis, the characteristic hiccup sound occurs. […] Scientists are still speculating about the precise mechanism responsible for hiccups, as well as how exactly capsaicin leads to spasms of the diaphragm, which, at this point, remains unclear.

• #1 Hiccup: Mystery, Nature and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3325297/

  The effective hiccup treatment is exactly established upon a correct diagnosis of lesion responsible for the serious event. […] Gabapentin, an alpha-2-delta ligand with structural similarity to GABA and the ability to block voltage-operated calcium channels to reduce release of several neurotransmitters including glutamate and substance P and finally to modulate the diaphragmatic activity, was promising and safe to treat intractable hiccups. […] Phrenic nerve blockades such as ultrasound guided blocking of efferent limbs, trans-esophageal diaphragmatic pacing and nerve stimulator to confirm the effective blocking were successfully used to treat persistent post-operative and lung cancer related hiccups. […] Hiccup usually results from a lesion involving the hiccup reflex arc.

• #2 Hiccups: a common problem with some unusual causes and cures

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5072913/

  Hiccups is a reflex consisting of a sudden spasmodic contraction of the diaphragm causing shaking of the inspiratory muscles of the chest and abdomen, followed by the sudden closure of the glottis, which generates a characteristic noise of air being violently expelled from the lungs. The hiccup reflex consists of the afferent limb (phrenic nerve, vagus nerve, or thoracic sympathetic fibres), the central connection (not involving a specific centre), and the efferent limb (primarily the phrenic nerve). […] In the present case, the CXR guided us to the diagnosis and CT was needed to confirm the cause of persistent hiccups: an acute aortic syndrome that caused thoracic aortic enlargement due to an intramural aortic haematoma. This haematoma extended to partially occupy the aortopulmonary window and presumably caused compression of the phrenic nerve that stimulates the diaphragm, which was an initial symptom of the patient with hiccups. […] The purpose of these manoeuvres is the attempt to interrupt the reflex arc thought to maintain repetitive diaphragmatic contractions. […] To target the cause of hiccups, it is extremely important to obtain a thorough clinical history.

• #2 Hiccup: Mystery, Nature and Treatment

  https://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm.2012.18.2.123

  Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. […] A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. […] The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. […] The pathophysiological mechanism of hiccup is related to lesions in its reflex arc shown in Figure. […] The hiccup reflex arc consists of 3 components, the afferent limb including phrenic, vagus and sympathetic nerves to convey somatic and visceral sensory signals, the central processing unit in the midbrain and the efferent limb traveling in motor fibers of phrenic nerves to diaphragm and accessory nerves to the intercostal muscles, respectively.

• #2

  https://jhoponline.com/issue-archive/2014-issues/december-vol-4-no-4/16296-hiccups

  Hiccups occur secondary to an involuntary spasm of the diaphragm and intercostal muscles, which is followed by the sudden closure of the glottis generating the hic sound. These involuntary spasms occur at a rate of 4 to 60 per minute and predominantly involve the left hemidiaphragm. The pathogenesis of hiccups is complex with a variety of etiologies, resulting in the neurophysiologic effect of the condition. […] The hiccup reflex arc is composed of efferent and afferent limbs, as well as a central hiccup center. The nerves that are involved in this reflex include the vagus, phrenic, and elements of the sympathetic nervous chain primarily in the thoracic region. This chain of nerves can be activated at multiple points, making the true cause of an individual’s hiccups hard to discern and treat.

• #2 Neurotransmitters in hiccups | SpringerPlus | Full Text

  https://springerplus.springeropen.com/articles/10.1186/s40064-016-3034-3

  The central component for hiccups lies in the medulla and is thought to be entirely separate from the pathways involved in rhythmic breathing. […] Dopamine, gamma-amino-butyric-acid (GABA), serotonin, glutamate, and glycine neurotransmitters can regulate this central mechanism. […] The mechanism of action of hiccups might be mediated through agonizing 5-HT1A and antagonizing 5-HT2A receptors to enhance the activity of the phrenic nerve, thereby inducing hiccups. […] It is postulated in a study that the GABA-containing cells in the nucleus raphe are the source of GABA-nergic inhibition of the hiccup center. […] The reflex arc is potentially mediated by central neurotransmitters (GABA, dopamine, and serotonin) and peripheral neurotransmitters (epinephrine, norepinephrine, acetylcholine, and histamine). […] Further research is needed to characterize the neurotransmitters involved in hiccups for potential new therapeutic targets.

• #2 :: Journal of Neurocritical Care

  https://www.e-jnc.org/m/journal/view.php?doi=10.18700/jnc.200018

  The efferent response of the reflex is carried by the phrenic nerve to the diaphragm. […] Various neurotransmitter pathways of the brainstem and medulla, including those involving dopamine, serotonin, opioids, calcium channels, and GABA are possibly involved in mediating hiccups. […] Any process that affects the peripheral afferent, central, or efferent components of the proposed reflex arc can trigger hiccups. […] Central hiccups could occur with any lesions along the pathway from the CNS to the phrenic nerve, especially with lesions of the brain stem, such as tumors and ischemic stroke. […] Chronic hiccups have been reported following hemorrhagic and ischemic strokes, cerebellar aneurysms, and neuromyelitis optica. […] The dorsal area of the medulla is commonly associated with hiccups as it incorporates a number of complex structures which conciliate the reflex arc, including the vagus nerve, respiratory center, solitary nucleus, nucleus ambiguus, central sympathetic tract, and spinal tract of trigeminal nucleus.

• #2 Hiccups, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17672-hiccups

  Hiccups happen when something irritates the nerves that cause your diaphragm to contract. These nerves, including your vagus nerve and phrenic nerve, make up a pathway that experts call a reflex arc. Reflex arcs manage your bodys involuntary functions. These are processes you dont consciously control (like breathing, digestion and heart rate). Irritation of the nerves that control your diaphragm can cause it to suddenly contract. […] Various medical conditions can cause persistent hiccups, including: Gastrointestinal diseases, like GERD or gastritis. Conditions affecting your central nervous system, like stroke, Parkinsons disease or multiple sclerosis. Lung conditions, like pneumonia, pulmonary embolism or pleurisy. Tumors or lesions, like mediastinal tumors, esophageal cancer or pancreatic cancer. Conditions that disrupt your metabolism and related nerve signaling, like uremia or hypocalcemia. Certain infections, like flu, shingles and herpes simplex.

• #2 Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172057

  Chemotherapy-induced hiccups were recently reported. A relationship was found between anti-cancer drugs and hiccups, and a large number of studies have described hiccups caused by cisplatin. […] The clinical features and mechanisms responsible for the pathogenesis of hiccups have been partially elucidated. However, drug-induced hiccups have not yet been cyclopedically examined and a unified view on the factors involved in hiccups does not exist. […] The multivariable analysis indicated that anti-cancer drugs and dexamethasone are independent risk factors for hiccups. Drug-induced hiccups are regarded as peripheral hiccups. The induction of hiccups by anti-cancer drugs has been attributed to peripheral neuropathy and direct irritation of the organ. Among the medications in this examination, platinum drugs including oxaliplatin and cisplatin are known to cause peripheral neuropathy.

• #2 Analysis of Factors Associated with Hiccups Using the FAERS Database

  https://www.mdpi.com/1424-8247/15/1/27

  This study revealed that hiccups as a side effect are more likely to occur in males, and it is suspected that the effects of the drugs differ by gender. […] The mechanism by which nicotine induces hiccups may thus be different from that of other drugs. […] The present study shows that the intake of nicotine other than by smoking can induce hiccups. […] These findings suggest that nicotine induces hiccups by releasing dopamine, which is involved in GABAergic inhibition. […] The effects of each suspect drug on receptor activity and neurotransmitter pathways were not elucidated in this study, and future studies in this regard are expected. […] This study suggests the new finding that the steroids dexamethasone and methylprednisolone are male-specific risk factors. […] The mechanism is not known. […] The risk factors for inducing hiccups in women were nicotine, dasabuvir, exenatide, sodium oxybate, and age.

• #2 Reddit – The heart of the internet

  https://www.reddit.com/r/todayilearned/comments/1jt0jkm/til_that_hiccups_may_reflect_our_amphibian/

  Hiccups may reflect our amphibian ancestry. The neural mechanism controlling hiccups closely resembles the breathing pattern generator in tadpoles, which helps them breathe through gills while keeping water out of their lungs.

• #2 Opinion: What causes hiccups and how can you get rid of them? | Western Sydney University

  https://www.westernsydney.edu.au/newscentre/news_centre/more_news_stories/opinion_what_causes_hiccups_and_how_can_you_get_rid_of_them

  Hiccups are caused by a reflex arc: a neuromotor pathway that translates a sensation into a physical response. The sensations in this arc come from the brain, ear, nose and throat, diaphragm and organs in the chest and abdomen. […] The sensation signals travel to a part of the brain which, along with the top of the spinal cord, is known as the hiccup centre. […] From the hiccup centre, the signals travel back out to the diaphragm and the muscles that lay between your ribs (intercostal muscles), causing them to twitch. […] Anything that affects the arc can lead to hiccups. The most common is stretching the stomach from eating a large meal or drinking soft drinks. This means sensation signals from the stomach can trigger off the reflex arc. […] Hiccups have even been observed in healthy fetuses during prenatal ultrasound checks. In fact, some researchers believe hiccups are a mechanism to help prepare the lungs for breathing shortly after birth.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Hiccups.aspx

  There are theories that the hiccup has a role in the gastrointestinal tract to remove air from the stomachs of young mammals this is thought because of the numerous gastrointestinal stimuli observed to elicit them. […] It is just as likely however that the hiccup is a vestigial reflex with a no longer present purpose. The cause of hiccups has been linked to the following: Alcohol consumption, Excessive smoking, A temporary swollen stomach this can be caused by overeating or eating too fast, drinking hot or carbonated drinks, or swallowing air, Eating too quickly or eating spicy foods, Sudden emotions, such as stress, fear or excitement, Any illness that irritates the nerves that control the diaphragm, Hyperventilation (because this is when carbon dioxide levels in the blood decrease). […] It is possible for certain disorders to trigger long-term hiccups. These can interrupt the bodys usual control of the hiccup reflex and can include: Encephalitis, Alcoholism, Meningitis, Multiple sclerosis, Stroke, Traumatic brain injury, Tumors, Particular drugs such as barbiturates, anesthesia (following procedures particularly if they involve abdominal organs), corticosteroids, benzodiazepines and tranquilizers.

• #2

  https://jhoponline.com/issue-archive/2014-issues/december-vol-4-no-4/16296-hiccups

  Intractable hiccups can result in anxiety, increased depression, sleep loss, impaired nutrition and fluid intake, aspiration, and induction of cardiac arrhythmias via activation of underlying cardiac pathology. This may result in significant impairment, and more rarely, death of the patient. […] The only US Food and Drug Administration approved hiccup remedy is chlorpromazine, which may not be useful in many patients because of its associated side effects. […] Many agents have been tried, with anecdotal success, and are hypothesized to work via a variety of neural mechanisms to decrease the activity of irritated nerves via sodium, calcium, or gamma-aminobutyric acid (GABA)-enervated pathways. […] Currently, there is little guidance on which agent should be used initially for hiccups of different etiologies. Because of the larger body of literature, most practitioners use chlorpromazine, metoclopramide, or baclofen as the initial treatment modality; a trial of multiple single agents or combinations of agents is also common.

• #2 Hiccups: What Are They, and How Can We Stop Them?

  https://www.contemporaryclinic.com/view/hiccups-what-are-they-and-how-can-we-stop-them-

  Hiccups are brief, involuntary, and irregular bursts of air that are really 2 different events causing 1 hiccup. First, there is an involuntary contraction of the diaphragm, the muscle at the base of the lungs. The second event is the closing of the glottis. It is here that the vocal cords are located, causing the „hic” sound. […] The results of a 2012 systemic review found that 1% to 9% of patients with advanced cancer experienced intractable or persistent hiccups. […] Below are a few examples of risk factors that cause hiccups. Additionally, a thorough assessment and physical examination can help determine the cause. […] Pharmacotherapy may be considered for intractable and persistent hiccups. The drug choice will be based on the underlying cause, and because this can vary among patient, the medication chosen will also vary. […] Hiccups are generally harmless but can cause distress and inconvenience. Obtaining knowledge on the science behind and causes of hiccups provide insight on how to treat this peculiar occurrence.

• #2 Remedies for Hiccups: What to Do & When to See a Doctor

  https://www.webmd.com/a-to-z-guides/remedies-for-hiccups

  Sometimes, people get hiccups after abdominal surgery. This could be because this kind of surgery can affect your stomach muscles, slowing down your ability to digest food. As a result, food stays in your stomach longer. It also might be because anesthesia can lead to hiccups. […] If you experience long-term, or chronic, hiccups, your doctor might prescribe you a medicine called baclofen. Baclofen is an effective treatment for hiccups because it relaxes your muscles. Keeping your muscles relaxed helps calm your body and settle your diaphragm. […] According to traditional Chinese medicine (TCM), putting pressure on certain parts of the body could ease your hiccups. […] In TCM, this particular pressure point is indirectly connected to the diaphragm by energy channels. In Western medicine, the area of skin covering this pressure point is linked to the diaphragm through nerves.

• #2 Demographic and Clinical Risk Factors of Hiccups

  https://www.gavinpublishers.com/article/view/demographic-and-clinical-risk-factors-of-hiccups

  Hiccups are caused mainly by diaphragmatic myoclonus, a brief involuntary twitching of the diaphragmatic muscles, together with coordinated contraction of the glottic closure group of muscles. […] While the clinical features and pathogenesis of hiccups have been partially elucidated, there has been no complete physical examination of the associations between hiccups and clinical variables such as primary disease. […] We suggest that low BMI is a reliable physical index related to hiccup risk, while chemotherapy and certain malignant tumors are clinical risk factors. These results may assist in elucidating the underlying mechanisms and guiding therapy to reduce hiccup risk. […] We report for the first time that BMI is an independent risk factor for hiccups in patients above 40 years old. We also confirmed that chemotherapy, certain malignant tumors, and neurovascular diseases are risk factors. These results may enable the identification of high-risk patients and treatment regimens, thereby reducing risk and improving quality of life. Moreover, such information may help clarify the pathomechanisms of hiccups.

• #2 What causes hiccups and how can you get rid of them?

  https://theconversation.com/what-causes-hiccups-and-how-can-you-get-rid-of-them-196557

  One study from France found 80% of patients with chronic hiccups had abnormalities in their oesophagus and stomach, with reflux disease being the most common finding. […] After a thorough investigation, the underlying cause should be treated, where possible. […] Other medications with a strong evidence base that are used to treat hiccups include the anti-nausea drug metoclopramide and baclofen, which is used to treat muscle spasticity (excessive tightness or tone). […] FISST is thought to stop the hiccup reflex arc by stimulating the sensory nerves to cause contraction of the diaphragm and glottis.

• #2 Opinion: What causes hiccups and how can you get rid of them? | Western Sydney University

  https://www.westernsydney.edu.au/newscentre/news_centre/more_news_stories/opinion_what_causes_hiccups_and_how_can_you_get_rid_of_them

  If hiccups last longer than two days, they are called persistent hiccups. If they last beyond two months they are known as intractable hiccups. Persistent and intractable hiccups, known collectively as chronic hiccups, can be quite distressing and may signify a serious underlying cause, so its important to see your doctor. […] One study from France found 80% of patients with chronic hiccups had abnormalities in their oesophagus and stomach, with reflux disease being the most common finding. […] After a thorough investigation, the underlying cause should be treated, where possible. […] Other medications with a strong evidence base that are used to treat hiccups include the anti-nausea drug metoclopramide and baclofen, which is used to treat muscle spasticity (excessive tightness or tone). […] FISST is thought to stop the hiccup reflex arc by stimulating the sensory nerves to cause contraction of the diaphragm and glottis.

• #2 Hiccups as the first presentation of secondary adrenal insufficiency associated with advanced cervical cancer in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2022 Issue 1 (2022)

  https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM22-0286.xml

  Hiccup is defined as an intermittent spasmodic contraction of the diaphragm. […] Pathological hiccups occur when one of these pathways is compromised, and they can be divided into four categories depending on the causative lesion. […] Hyponatremia, which is one of the causes of hiccups, is seen in 47% of patients with advanced cancer. […] AI is one of the main causes of hyponatremia in patients with advanced cancers. […] If hiccups occur in patients with advanced cancer, the differential diagnosis should include hyponatremia.

• #2 Intraoperative Laryngeal Mask Airway-Related Hiccup: An Overview

  http://www.transpopmed.org/articles/tppm/tppm-2019-7-103.php

  Vagus nerve innervates the pharynx and upper esophagus and it is postulated that stimulation of the vagus nerve while insertion or rapid inflation of the laryngeal mask airway acts as a trigger for initiating hiccups. […] The pathophysiology of gastroesophageal reflux in most patients with GERD revolves around transient or lasting LES relaxation. […] Considering the pressure difference across LES is responsible for reflux after hiccup, it is also likely that patients with GERD might be at increased risk of developing hiccup. […] The incidence of laryngeal mask airway -related hiccup is estimated to be around 5%. […] Different models of laryngeal mask airway may have different impact on the incidence of laryngeal mask airway -related hiccup. […] The external larynx lift technique was found to be potentially less likely to cause tissue trauma of the upper airway during laryngeal mask airway insertion.

• #2 Demystifying the Relationship Between Alcohol and Hiccups – Alis Behavioral Health

  https://www.alisbh.com/blog/hiccups-when-drunk/

  Several factors related to alcohol consumption contribute to the hiccup reflex. Among these factors are a distended stomach and rapid temperature changes, both of which can stimulate the vagus and phrenic nerves and initiate hiccups. Drinking alcohol, particularly in large quantities, can lead to stomach distension, especially when consuming carbonated beverages or beer. This distension can trigger the hiccup reflex, causing hiccups to occur. […] Understanding the mechanism of alcohol-induced hiccups and the contributing factors can help individuals better comprehend why hiccups may occur after drinking alcohol. While hiccups caused by alcohol consumption are generally temporary and resolve on their own, it’s important to recognize when seeking medical attention is necessary, as persistent or chronic hiccups could indicate underlying health issues.

• #2 Systemic review: the pathogenesis and pharmacological treatment of hiccups

  https://www.zora.uzh.ch/id/eprint/113704/

  Hiccups are familiar to everyone, but remain poorly understood. […] Management was most effective when directed at the underlying condition. An empirical trial of anti-reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well-designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo-controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long-term therapy. […] Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve.

• #3 Neurotransmitters in hiccups | SpringerPlus | Full Text

  https://springerplus.springeropen.com/articles/10.1186/s40064-016-3034-3

  Hiccups are the sudden involuntary contractions of the diaphragm and intercostal muscles. […] The hiccup reflex arc is composed of three components: (1) an afferent limb including the phrenic, vagus, and sympathetic nerves, (2) the central processing unit in the midbrain, and (3) the efferent limb carrying motor fibers to the diaphragm and intercostal muscles. […] Data obtained largely from case studies of hiccups either induced by or treated with medications have led to hypotheses on the neurotransmitters involved. The central neurotransmitters implicated in hiccups include GABA, dopamine, and serotonin, while the peripheral neurotransmitters are epinephrine, norepinephrine, acetylcholine, and histamine. […] The pathophysiological mechanism of hiccups is related to lesions in its reflex arc.

• #3 Hiccups: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/775746-overview

  Hiccups appear to serve no purpose in humans or other mammals. Often, only a single hemidiaphragm is affected. The left hemidiaphragm is affected in 80% of cases, though bilateral involvement may occur. […] Despite centuries of contemplation, the exact pathogenesis of hiccups remains a mystery. Hippocrates and Celsus associated hiccups with liver inflammation and other conditions. Galen believed that 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: Afferent limb: Phrenic and vagus nerves and sympathetic chain arising from T6 to T12; Hiccup center: Nonspecific location between C3 and C5; Connections to the respiratory center, phrenic nerve nuclei, medullary reticular formation, and hypothalamus; Efferents: Phrenic nerve (C3-5), anterior scalene muscles (C5-7), external intercostals (T1-11), glottis (recurrent laryngeal component of vagus), inhibitory autonomic processes, decreasing esophageal contraction tone, and lower esophageal sphincter tone.

• #3 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Hiccups.aspx

  Hiccups are experienced by almost everyone during their lives bouts of hiccups have even been shown to occur in fetuses in utero and in a wide variety of animals. The medical term given for hiccups is „singultus”. […] The physiology behind the hiccup is complicated. This motor action is an involuntary reflex controlled by the medulla it involves the coordinated action of the diaphragm, the muscles that govern the opening and closing of the trachea and the nerves that innervate these muscles. It seems that there is a hiccup center in the medulla from where efferent nerve fibers travel to the diaphragm. […] In a hiccup, the firing of this center leads to the intense activation of the respiratory muscles followed by the rapid closure of the glottis. This closure occurs approximately 35 milliseconds after the activation and with a noise produced at the top of the trachea that is the characteristic hiccup sound.

• #3 :: Journal of Neurocritical Care

  https://www.e-jnc.org/m/journal/view.php?doi=10.18700/jnc.200018

  Hiccups are usually self-limiting and benign but can be distressing when they become persistent or intractable and produce significant morbidity. […] Though persistent hiccups which are intractable and of neurogenic origin can result in hyperventilation and respiratory alkalosis, and are a risk factor for ventilator associated pneumonia in intubated and mechanically ventilated patients. […] The mechanism of hiccups is not very clear and the neuroanatomical center for hiccups has not been identified, though few hiccups provoking hypothesis have been proposed. […] The afferent impulse in this proposed arc is carried by the vagus nerve, phrenic nerves, or sympathetic nerve fibers (thoracic outflow T6T12). […] Dopaminergic and gamma-aminobutyric acid (GABA)ergic neurotransmitters are involved in the modulation of this central mechanism.

• #3

  https://journals.lww.com/jopn/fulltext/2022/17020/carbamazepine_induced_hiccups__a_case_report.17.aspx

  Carbamazepine (CBZ) is a tricyclic compound that is most efficient against partial seizure with or without secondary generalization. It acts by inhibiting voltage-gated sodium channel, thereby preventing repetitive and sustained firing of action potential. […] Hiccup is an involuntary, intermittent, spasmodic contraction of the diaphragm and inspiratory muscles resulting in sudden inspiration and ending with abrupt closure of the glottis, followed by a peculiar sound. Hiccups can arise from idiopathic, psychogenic, and organic causes. Drug-induced hiccup is a rare entity and require investigation for other causes or underlying pathologies. […] Although the exact mechanism by which hiccups develop is poorly understood, a central component of the hiccup reflex arc is situated in the medulla. Serotonin, dopamine, -aminobutyric acid (GABA), glutamate, and glycine neurotransmitters can regulate this central mechanism of hiccups. This reflex arc is also regulated by input from catecholaminergic and serotonergic afferents.

• #3 Hiccups, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17672-hiccups

  Hiccups happen when something irritates the nerves that cause your diaphragm to contract. These nerves, including your vagus nerve and phrenic nerve, make up a pathway that experts call a reflex arc. Reflex arcs manage your bodys involuntary functions. These are processes you dont consciously control (like breathing, digestion and heart rate). Irritation of the nerves that control your diaphragm can cause it to suddenly contract. […] Various medical conditions can cause persistent hiccups, including: Gastrointestinal diseases, like GERD or gastritis. Conditions affecting your central nervous system, like stroke, Parkinsons disease or multiple sclerosis. Lung conditions, like pneumonia, pulmonary embolism or pleurisy. Tumors or lesions, like mediastinal tumors, esophageal cancer or pancreatic cancer. Conditions that disrupt your metabolism and related nerve signaling, like uremia or hypocalcemia. Certain infections, like flu, shingles and herpes simplex.

• #3 Vagal Nerve Stimulation for Intractable Hiccups | Suliman | Journal of Neurology Research

  https://www.neurores.org/index.php/neurores/article/view/792/755

  Intractable hiccups are those lasting beyond a month; they can lead to significant morbidity. […] A number of cases have been described of the utility of vagal nerve stimulation in treating intractable hiccups. Here we outlined the indications as well as hypothesized mechanism of action. […] The pathophysiology of hiccups remains unclear, but it is thought to be a reflex response with several neural pathways being involved. […] The afferent limb of the reflex arc includes the phrenic nerve, the vagus nerve and the sympathetic chain (T6 – T12). […] The central nervous system (CNS) mediators involved in the hiccup response are believed to be the medulla oblongata and the spinal cord segments C3 – C5, with possible modulation from hypothalamus, midbrain, reticular activating system, the respiratory center, globus pallidus, subthalamic nucleus, temporal lobes and nuclei of phrenic nerves.

• #3 What causes hiccups and how can you get rid of them?

  https://theconversation.com/what-causes-hiccups-and-how-can-you-get-rid-of-them-196557

  Hiccups are caused by a reflex arc: a neuromotor pathway that translates a sensation into a physical response. […] The sensation signals travel to a part of the brain which, along with the top of the spinal cord, is known as the hiccup centre. […] From the hiccup centre, the signals travel back out to the diaphragm and the muscles that lay between your ribs (intercostal muscles), causing them to twitch. […] Anything that affects the arc can lead to hiccups. […] Hiccups have even been observed in healthy fetuses during prenatal ultrasound checks. […] In fact, some researchers believe hiccups are a mechanism to help prepare the lungs for breathing shortly after birth. […] Persistent and intractable hiccups, known collectively as chronic hiccups, can be quite distressing and may signify a serious underlying cause, so it’s important to see your doctor.

• #3 Hiccups | Pregnancy Birth and Baby

  https://www.pregnancybirthbaby.org.au/hiccups

  Hiccups, also called hiccoughs, are a familiar condition in babies and adults. Hiccups are caused when the diaphragm (the thin muscle between the chest and the abdomen) involuntarily contracts and tightens. […] Once the nerves in the diaphragm are triggered, the diaphragm goes into spasms. Its not clearly understood what causes the nerves to be stimulated in the first place. Though in babies, hiccups are generally understood to be due to feeding. […] Its understood the mechanism for hiccupping is the same for people of all ages from babies to adults. The involuntary, sharp contraction of the diaphragm causes a sharp intake of air into the throat. As the epiglottis (a flap at the top of the airway) closes, it makes the hic sound. […] Hiccups that last for days, weeks or even years may be symptomatic of underlying disease.

• #3 The hiccup remains a mystery, though there are many theories about its causes and cures – The Washington Post

  https://www.washingtonpost.com/national/health-science/the-hiccup-remains-a-mystery-though-there-are-many-theories-about-its-causes-and-cures/2014/06/02/c282af74-b8fd-11e3-899e-bb708e3539dd_story.html

  Another theory posits that hiccups date all the way back to our amphibian ancestors. […] What is agreed upon and well known, however, is the mechanism of a hiccup. Referred to in medicine as singultus, it is defined by a sudden contraction of the diaphragm and intercostal muscles — located within the spacing between the ribs — followed by snapping shut of the glottis, the space between the vocal folds within the larynx. The quick spasm of inhalation colliding with the closed larynx causes the characteristic sound and bodily jerk. […] Most experts also agree that hiccups involve a neuronal circuit starting with the phrenic and vagus nerves. The vagus nerve extends from the brainstem to the abdomen, while the phrenic nerves send signals from the brain to the diaphragm. […] But he says most people don’t need to worry unless the hiccups interfere with respiration or eating. […] “Everybody gets them, but we don’t know why — we don’t know if [in terms of evolution] it’s adaptive or maladaptive,” Cymet said. “We’re still in the dark ages of understanding hiccups.”

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