Hiccups are a common condition that many general practitioners do not fully understand or adequately manage. However, it is essential to recognise that hiccups should not be dismissed, as they may indicate significant medical conditions.

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The hiccups are something that almost everyone has experienced at some point in their lives. The Roman word "singult," meaning "to catch one's breath while crying," is the origin of the medical term "singultus." An involuntary and abrupt contraction of the diaphragm and intercostal muscles causes hiccups. When the vocal cords have contracted, the glottis will close suddenly, resulting in a "hic" sound. These episodes often last less than 48 hours and go away on their own.

Hiccups can be classified into three stages based on duration: acute (less than 48 hours), chronic (over 2 days), and intractable (more than 1 month). They can have various underlying causes, such as:

• Problems in the digestive tract, such as gastro-oesophageal reflux
• Negative drug interactions
• Conditions affecting the heart, brain, or neurological system
• Problems with the ear, nose, or throat
• Psychological or metabolic abnormalities

This exercise explores the complete range of hiccup symptoms, from mild to severe, discusses their origins, and suggests medical interventions based on the specific case of the patient.

Persistent and intractable hiccups may have a substantial effect on the quality of life by disrupting eating, sleeping, speaking, and social activities and can be a precursor to more severe medical pathology.

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Possible causes of hiccups

1. Gastrointestinal issues, including gastro-oesophageal reflux disease (GERD) and hiatus hernias

1. Studies have shown that up to 10% of people with GERD also have hiccups.
2. Stomach distention after consuming large meals, fizzy drinks, and spicy or alcoholic foods can also cause hiccups.
3. Almost one-quarter of individuals with oesophagal tumours will also have chronic choking.

2. Psychological factors

Extreme excitement or anxiety, particularly if accompanied by excessive breathing or air swallowing, can trigger hiccups.

3. Substance use

1. Alcohol and other substances have been linked to tachycardia, which can cause hiccups.
2. Certain medications, such as benzodiazepines, glucocorticoids, and chemotherapeutic drugs, have been linked to an increased risk of hiccups.
3. Benzodiazepines have been shown to cause hiccups even at low doses, but may also help relieve hiccups in larger quantities.
4. Chemotherapeutic drugs, alpha-methyldopa, and inhalation anaesthetics have also been linked to hiccups in certain patients.

4. Other medical conditions

Cardiovascular problems, central nervous system (CNS) disorders, ENT disorders, and metabolic/endocrine disorders have all been reported to cause chronic, intractable hiccups.

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Prevalence

Older men and those who are taller or heavier are more likely to have intractable hiccups, as shown by an odds ratio of 2.4. Parkinson's disease and other central nervous system illnesses, advanced cancer, where the incidence may be as high as 4-9%, and gastro-oesophageal reflux disease, where the incidence may be as high as 8- 10% are associated with an increased risk of persistent hiccups (GERD).

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How to assess

1. Examining a patient with hiccups requires a careful evaluation of their medical history.
2. Inquire about provoking factors such as heavy meals, emotional stress, or enthusiasm, as well as any accompanying symptoms such as gastric reflux, stomach discomfort, coughing, or weight loss.
3. Ask about any neurologic symptoms that could indicate Parkinson's disease, multiple sclerosis, or a medullary stroke.
4. Hiccups during sleep may be caused by pulmonary, neurologic, or gastric diseases and can rule out a psychological origin.
5. Inquire about chemotherapy, recent surgery, and known cancers.
6. A thorough assessment of all medications may reveal a plausible culprit, and if stopping the problematic drug results in appreciable alleviation, causation is established.
7. Investigate organic reasons if the hiccups are chronic and uncontrollable.
8. A thorough ENT examination may identify conditions like goitres, tumours, tonsillitis, pharyngitis, or a foreign object pushing on the tympanic membrane.
9. While evaluating for thoracic reasons like pneumonia or empyema, pay attention to the lung sounds.
10. Palpitate the abdomen for pain or mass to rule out the blockage, volvulus, pancreatitis, hepatitis, or mass.
11. A thorough neurological examination may reveal CNS diseases such as tumours and strokes, though it is uncommon for hiccups to be the sole presenting symptom.

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What to investigate

1. Conduct a comprehensive investigation to find a treatable cause of chronic and intractable hiccups.
2. Order lab tests to rule out infectious and neoplastic processes that were missed during the history and physical examination or to evaluate electrolyte abnormalities.
3. Do laboratory testing for electrolytes, calcium, blood urea nitrogen (BUN), creatinine, lipase, and liver function.
4. Find intractable causes of the hiccups such as pneumonia, empyema, diaphragmatic hernia, adenopathy, or aortic disease with a chest radiograph.
5. Brain imaging by computed tomography (CT) or magnetic resonance imaging (MRI) may reveal reasons such as stroke, multiple sclerosis, tumour, syringomyelia, neuromyelitis optica, aneurysm, or vascular malformation for recurrent or intractable hiccups coupled with neurologic symptoms or signs.
6. Cerebrospinal fluid may sometimes be required to rule out meningitis or encephalitis.
7. Thoracic or abdominal CT imaging may sometimes reveal malignancy, aneurysm, abscess, or a hernia.
8. Refer patients to gastroenterology for an upper endoscopy to exclude lesions (such as oesophagal cancer) in situations with persistent hiccups that don't respond to the first antacid and proton pump inhibitor medication.
9. Check blood gases for each ventilated patient who has hiccups.
10. Patients on ventilators who have hiccups run the risk of hemodynamic abnormalities, severe breathing disturbances, and ventilator resynchronisation.

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How to manage

Physical manoeuvres for alleviating hiccups

A range of basic physical manoeuvres, backed by anecdotal evidence, are likely to alleviate hiccups in the acute phase. The majority of the movements target a section of the hiccup reflex arc. When PCO2 increases, the frequency of hiccups decreases, making Valsalva, breath holding, and breathing into a paper bag potentially helpful. Supra-supramaximal inspiration is a method in which the subject fully exhales, inhales deeply, holds the breath for 10 seconds, and then inhales twice more, holding each breath for 5 seconds.

Managing chronic and intractable hiccups

Other methods include using cold beverages, pulling on the tongue, applying pressure to the carotid arteries, the eyes, or both external auditory canals, consuming vinegar or sugar, stimulating the uvula or posterior nasopharynx (using smelling salts or nasal vinegar), performing the Valsalva manoeuvre, or gargling, gagging, or even self-inducing vomiting. Suboccipital release and osteopathic/chiropractic manipulation procedures have been reported. These methods all seem to work significantly better in the acute period. Often complex and more difficult to cure, the persistent phase.

Assessing if a patient is taking a medicine known to cause hiccups and figuring out whether hiccups are linked to GERD are crucial initial steps in treating chronic and intractable hiccups. Medication-induced hiccups may be treated by stopping the offending drug or using an alternative treatment (such as switching from dexamethasone to methylprednisolone). A first treatment trial with antacids, antihistamines (like famotidine), or proton pump inhibitors (like omeprazole) may be helpful with as many as 80% of persistent hiccup instances associated with GERD, and this method has been advised as first-line therapy.

Pharmacotherapy for persistent hiccups

The majority of investigations have examined pharmacotherapies that affect one or more reflex arc components during the persistent phase. Pharmacotherapy, which targets neurotransmitters, is divided into central and peripheral therapies, while some have dual effects. The neurotransmitters GABA, dopamine, and serotonin are involved in central processing. These include acetylcholine, histamine, epinephrine, and norepinephrine in the periphery.

Chlorpromazine has traditionally been the preferred medication for persistent hiccups, and it is still the sole medication for hiccups recognised by the U.S. Food and Drug Administration (FDA). Dopamine, serotonin, histamine, alpha-adrenergic, and muscarinic receptors are just a few of the neurotransmitter sites on which chlorpromazine works as an antagonist.

Metoclopramide, the GABA agonists baclofen and gabapentin, and medications for chronic or intractable hiccups are the most often investigated medications. These three medications have fewer adverse effects than conventional antipsychotics. Metoclopramide, gabapentin, or baclofen are acceptable second-line treatments if no cause is discovered after a comprehensive examination. Metoclopramide has been effective in treating hiccups caused by cancer, stroke, and brain tumours. It works centrally as a dopamine antagonist and peripherally by improving stomach motility.

Baclofen has been shown beneficial for idiopathic causes without gastric illness and persistent hiccups in stroke patients by acting to reduce neuroexcitation and produce muscular relaxation. Similar to GABA, gabapentin reduces neuroexcitation by interacting with voltage-gated calcium channels and reducing the release of excitatory neurotransmitters. Gabapentin has been shown in one case series to be 66 to 88% effective in treating cancer and brainstem stroke patients.

Drugs investigated for hiccup treatment

A number of drugs, including amantadine, amitriptyline, antipsychotics (haloperidol, risperidone, olanzapine), atropine, benzonatate, carvedilol, glucagon, ketamine, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid, have been recommended for the treatment of persistent hiccup. Several injectable medicines, including atropine, ephedrine, dexmedetomidine, ketamine, and lidocaine, have been used to treat intraoperative hiccups. Other local anaesthetic administration techniques include subcutaneous infusions, oral viscous lidocaine, and lidocaine gel in the external auditory canal.

More intrusive treatment methods

More intrusive treatment methods include acupuncture, positive pressure breathing, vagus nerve stimulators, and stellate or phrenic nerve block for instances that don't respond to medication therapy. Limited studies have shown acupuncture to be effective in treating persistent hiccups in patients with cancer and stroke. It could be a viable choice for certain individuals who are too ill or old to undergo medication or more invasive procedures given the comparatively low complication rate with a possible benefit.

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An interesting case

The case

A 62-year-old man with hypertension, type II diabetes, and a cerebrovascular injury visited the ED after a week of hiccups. His primary care doctor prescribed baclofen and omeprazole for his hiccups five days before the presentation. Despite these medications, he developed hiccups. He also reported occasional, burning epigastric pain and growing shortness of breath during the last week. He was healthy.

Diagnosis

His ECG revealed a sinus rhythm with a Q-wave and T-wave inversion in lead aVL and a normal chest X-ray. His high-sensitivity troponin I level went from 1,883 to 2,183 ng/L in eight hours (normal: 2.5-53.48). Later, the cause was determined to be NSTEMI.

Treatment

The patient took aspirin, atorvastatin, carvedilol, ramipril, and therapeutic subcutaneous enoxaparin until his cardiac catheterisation the following day. Pantoprazole, magnesium hydroxide and aluminium hydroxide did not help his hiccups.

Coronary angiography revealed 90% stenotic proximal right coronary artery (RCA). Coronary artery stenting was done. His hiccups stopped after therapy, and he had no issues.

Causes and mechanism

Myocardial ischemia may cause hiccups, especially in the RCA and inferior walls. Ischemia damage to the myocardium activates the reflex arc's afferent limb—the sympathetic, vagus, and phrenic nerves. Due to its proximity to the phrenic nerve, which innervates the pericardium, cardiac ischemia of the inferior wall may irritate the vagus nerve.

Hiccups often linger longer while being innocuous and self-limiting. ACS, which damages the RCA and inferior myocardial wall, may cause recurrent hiccups. Given the severe morbidity and mortality of ACS, recurrent hiccups in older patients and those with risk factors should be further assessed.

Hiccups may be eliminated by treating cardiac ischemia. This example underscores the need for an ACS workup in any patient with recurrent hiccups, especially those with a unique presentation, as ACS is frequently considered a must-diagnose.

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Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Monish Raut is a practising super specialist from New Delhi.