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Hiccups and their curious connection to cancer

Because hiccups can seem innocuous, they remain mysterious and surprisingly understudied, and yet, they’re one of the most common bodily experiences humans (and rats, squirrels, rabbits, cats, dogs and horses) have; even foetuses get them.

When we hiccup, the diaphragm involuntarily contracts and the vocal cords snap closed, producing the eponymous “hic” sound. These spasms usually disappear within a few minutes.

Compared with cancer’s existential threat and the brutal reality of treating it, hiccups are innocuous, banal and unserious. But these two experiences are, peculiarly, connected, reports The Atlantic.

As many as 40% of cancer patients deal with bouts of hiccups during their illness. For a smaller subset, about one in 10, those spells last for more than 48 hours. In one woman, they lasted for nearly a year.

Chronic hiccups interrupt almost every aspect of life. They disrupt concentration and conversations. They shake a person awake. Eating, drinking and swallowing can feel like choking. Often, chest aches linger long after a hiccuping fit subsides.

And they are difficult to treat. Doctors have some off-label prescriptions at their disposal, but none has been rigorously tested, none has proved to work any better than home remedies.

Deep, forceful inhales and drinking water from the far rim of a glass are common efforts to end the bout: some people train themselves to exhale before drinking or eating to limit the amount of air swallowed.

Many try chiropractice or acupuncture. Others recruit household items: sugar, lemons, vinegar, a pencil, a cold spoon. Only one hiccup drug has ever been approved by the US Food and Drug Administration (FDA).

Hiccups, one of the most basic physiological features of human life, remain deeply mysterious and surprisingly understudied – partly because their fleeting nature makes them hard to examine, partly because they just seem so harmless. But when they’re not, hiccups confront us with how helpless we can be against our own body’s whims.

“There’s really no benefit to a hiccup, as far as anyone knows,” said Aminah Jatoi, a Mayo Clinic oncologist who studies hiccups. A transient symptom that appears and disappears randomly, hiccups are nearly impossible to study with rigour.

Experiments on treatments are, accordingly, a nightmare to orchestrate. To date, only a handful of randomised, controlled trials have studied pharmacological treatments for hiccups; none recruited more than 40 patients. Most studies rely on storytelling: single-patient case reports, limited case series, and analyses of databases of doctors’ notes.

What we do know

A sudden temperature shift can induce hiccups, as can drinking alcohol, eating spicy food, and getting excited or stressed. High blood sugar can be to blame. So can low sodium or electrolytes.

Many drugs, including steroids, chemotherapy agents, benzodiazepines, opioids, nicotine, antibiotics, anaesthesia, and anti-nausea and blood-pressure medicines, are linked with hiccups. Some drugs used to treat intractable hiccups can cause hiccups.

In one case study, a patient’s hiccups were incited by a hair brushing against the eardrum; in another, from 1988, the culprit was an ant crawling around the eardrum.

The medical conditions associated with hiccups range the body’s entire upper half: stroke, brain injury, meningitis, multiple sclerosis, ear infection, rhinitis, goitres, sore throat, pneumonia, bronchitis, asthma, tuberculosis, fluid in the lungs or heart, bloating, gas, pregnancy, hernias, ulcers, liver disease, kidney disease. And cancer.

Experts offer two main explanations for the cancer-hiccup connection.

In one, cancers that invade the chest, throat, or head (that is, anything along the route of a hiccup) provoke them. In the other, medications prescribed to cancer patients – including chemotherapy drugs, steroids and opioids – set them off.

Regardless of whether cancer itself is to blame or whether they’re a side effect of treatment, hiccups add another layer of misery to the experience.

One study published in 2022 showed that hiccups were a major detriment to the quality of life of about one in 20 of the cancer patients surveyed. Among those with hiccups, almost one in three said they struggled to relax or recreate; a smaller portion said they couldn’t enjoy meals.

In another study of 320 cancer patients, hiccups sent one in 10 to the hospital for help. Other research suggests that upwards of three-quarters of hiccup-struck patients deal with the spasms without medical intervention.

In a survey of 90 cancer-health-care providers with experience with hiccups, 40% rated their patients’ hiccup severity as worse than their nausea and vomiting.

Even so, experts say, hiccups remain an aside for both patients and practitioners.

Given the rapidity of physician visits – on average about 23 minutes, by one measure, for patients with cancer – hiccups may simply fall too low on a list of preoccupations to warrant mention, but “I think part of what happens is patients feel a little embarrassed bringing it up”, Jatoi said.

“Or the patient may want to be a ‘good’ patient and not complain,” says Thomas Smith, an oncologist and palliative-medicine specialist at Johns Hopkins – perhaps because they fear their doctors will modify their treatment course if they speak up about any negative side effects.

Oncologists, for their part, don’t consistently or directly ask about hiccups in the way that they screen for pain, nausea, and trouble breathing. “I don’t know of a single symptom-assessment scale in use that has a line for hiccups,” Smith said. Some brush off patients who do complain of the spasms.

And so hiccups are relegated to the category of “orphan” symptoms: prevalent, distressing, characteristically unaddressed. Other such symptoms include muscle cramps, itchiness, muscle twitching, restless legs syndrome, loss or distortion of taste, dry mouth, and sweating.

The success of palliative care depends on alleviating orphan symptoms: Every hiccup or itch or tingling foot, every flush of sweat or bout of constipation tethers patients to a raw state of awareness.

“It’s a common reminder that you have chemotherapy, which is a constant reminder you have cancer, which is a constant reminder you’re facing your mortality,” Smith said.

Treating hiccups offers medical relief in the form of escape. “It may make it possible for patients to have a few hours where they don’t think about cancer.”

Jatoi said she often warns patients who are about to start a potentially hiccup-inducing regimen. “That helps patients speak up,” she said, which is a step toward finding relief.

Oncologists can try prescribing a muscle-spasm treatment, for example, an off-label use that seems to help some patients. They might tweak the chemotherapy regimen to swop in drugs less likely to cause hiccups.

The one treatment for hiccups that the FDA has approved – chlorpromazine, an antipsychotic first synthesised 72 years ago – can come with serious side effects, which include low blood pressure and delirium.

Without clinically proven solutions, most hiccup sufferers are shepherded toward home remedies: breath-holding; drinking through hard-to-suck straws; swallowing spoonfuls of sugar, peanut butter, or vinegar.  “None has been tested to see how effective they are,”  Smith said.

But without solid alternatives, he added, they’re worth trying. After all, unlike the hiccups themselves, “they’re completely harmless.”

Study details

Frequency and Symptomatology of Hiccups in Patients With Cancer: Using an On-Line Medical Community to Better Understand the Patient Experience

Christopher Ehret, Colleen Young, Christine J. Ellefson, Lee A. Aase, Aminah Jatoi

Published in the American Journal Of Hospice And Palliative Medicine on 2 February 2022

Abstract

Background
Cancer patients are at risk for hiccups, but the incidence and impact on quality of life are unclear.

Methods
A survey (modified from the Functional Living Index with the inclusion of qualitative elements) was developed and launched on an 80,000-member medical social media platform, Mayo Clinic Connect https://connect.mayoclinic.org/.

Results
Among 213 respondents, 34 (16%; 95% CI: 11, 22%) reported “yes” that they had experienced hiccups with cancer therapy. Of those patients who reported hiccups, only 12 (35%) were men, and most were older than 50 years of age. Over 25% noted that hiccups occurred frequently around the time of cancer therapy; 30% described that hiccups interfered with their leisure or recreational activities; and over 15% described hiccups interfered with their ability to enjoy a meal. A few patients seemed to express frustration with hiccups with comments such as, “Totally uncontrollable,” “It’s extremely pain[ful] with throat cancer,” and “Once I had them so bad I almost choked.”

Conclusion
Hiccups occur in16% of patients who are receiving cancer therapy and, by our estimates and extrapolation, appear highly problematic in approximately 5%.

 

AHHPM article – Frequency and Symptomatology of Hiccups in Patients With Cancer: Using an On-Line Medical Community to Better Understand the Patient Experience (Open access)

 

The Atlantic article – Hiccups Have a Curious Connection to Cancer (Open access)

 

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