What Causes Hiccups in Cancer, and How Are They Treated?

Hiccups are involuntary contractions of the diaphragm, the muscle forming the base of our rib cage. They can sometimes be persistent and prolonged. In oncology and palliative care patients, persistent or temporary hiccups can be frustrating and exhausting. In cancer patients, they may occur at various stages because of the disease or its treatment.

Hiccups Develop in Up to 40% of Cancer Patients

Oncologists are often unaware of their patients' hiccups. According to a survey of cancer patients, however, even recognized hiccups may not be effectively treated.

When inadequately controlled, persistent hiccups can affect quality of life; 40% of respondents rated their chronic hiccups as "much worse" or "somewhat more severe" than nausea and vomiting.

Overall, the findings show that cancer patients developing persistent hiccups "really suffer."

Hiccups are experienced by everyone and generally resolve spontaneously. Episodes can result from rapid bloating after eating too much or too quickly; stomach irritation from spicy foods, carbonated drinks or swallowed air; sudden body temperature changes; alcohol, smoking or psychological factors. Charles Osborne, born in 1894, holds the Guinness record for the longest case: his hiccups began at 28 and lasted 68 years. With today's treatments, such a case no longer seems likely.

Hiccups can be classified by duration. Those lasting up to 48 hours are called a hiccup episode; those lasting from 48 hours to 1 month are called persistent hiccups; those lasting longer than 1 month are called intractable hiccups . Persistent and intractable hiccups can disrupt ordinary functions such as eating, drinking, speaking and sleeping. Consequently, weight loss, dehydration, insomnia, weakness-fatigue and psychological problems may develop, affecting quality of life. They can intensify pain in cancer patients. Because research involves limited patient numbers, data on frequency, race or geographical characteristics are unavailable. Hiccups are more common in men and children. In patients with advanced cancer (stage 4), intractable or persistent hiccups have been reported in 1-9%. One study suggested hiccups could be considered a symptom of esophageal cancer . According to Cleveland Medical Program data, hiccups were reported in 9% of palliative care patients.

Chemotherapy Is Not the Only Cause of Hiccups!

Causes can be divided into peripheral and central causes, further subdivided as follows:

Other causes include electrolyte and metabolic disorders (hyponatremia, hypokalemia, hypocalcemia, hypocapnia, kidney disorders), diabetes, alcoholism, psychological causes (anxiety, stress, fear), various medications and previous surgery. Drugs reported to cause hiccups include opioids (morphine derivatives), benzodiazepines, corticosteroids (cortisone drugs), dopamine agonists and some chemotherapy drugs. Many drugs causing hiccups are used in palliative care. Some also have a role in treating intractable hiccups.

Cancer itself can cause hiccups (esophageal, stomach, pancreatic and brain cancers), and the causes listed in the figure above can be encountered during cancer. Hiccups can also result from chemotherapy and radiotherapy.

Which Chemotherapy Drugs Most Commonly Cause Hiccups?

Chemotherapy drugs that can cause hiccups include:

• etoposide
• sispaltin
• carboplatin
• cyclophosphamide
• docetaxel
• gemcitabine
• irinotecan
• paclitaxel
• vindesine
• vinorelbine

How Are Hiccups Treated?

Before medication, non-drug treatments consisting of simple maneuvers should be considered. Familiar examples include holding the breath, drinking water, manually pulling out the tongue, straining, bending forward and drawing the knees toward the abdomen.

Most drugs used for hiccups act through the nervous system pathway called the GABAergic system. They include chlorpromazine, haloperidol, benzodiazepine, gabapentin, metoklorpromid and baclofen. Among them, chlorpromazine (brand name Largactil) is a drug many physicians consider first for hiccups. For cancer-related hiccups, taking a quarter (1/4) of a Largactil tablet is recommended; if hiccups persist, another dose is not recommended, and you should contact your oncology doctor or nurse. This drug, previously FDA (United States Food and Drug Administration)-approved for hiccups, later had its approval withdrawn because of hypotension, urinary retention (bladder tension due to inability to urinate) and delirium side effects. Although not currently a first-choice drug, some intractable cases respond.

Treatment should evaluate the causes described above. For example, hiccups due to gastric reflux are treated with medications reducing stomach acid secretion and accelerating gastric emptying.

Drugs containing metoklorpromid (Metpamid), baclofen, gabapentin, lidocaine, methylphenidate, midazolam or nimodipine may treat peripheral hiccups, but studies are insufficient to establish their efficacy.

A study of 14 patients with hiccups due to peripheral causes such as viral hepatitis, esophagitis and hemorrhagic (bleeding) gastritis showed marked efficacy of metklorpromid.

A study evaluating treatment responses in a patient with hiccups lasting eight months reported a good response to lansoprazole (reducing stomach acid), clonazepam and dimenhidrat when hiccups were thought related to a previous heart attack and reflux. Chlorpromazine, metoklorpromid and baclofen did not help in this case.

For central causes, treatment should again target the cause. For hiccups arising from a brain tumor, for example, surgical removal of the mass or radiotherapy would be options.

A randomized controlled study evaluated baclofen for intractable hiccups in 30 patients with brain damage from stroke. Baclofen was shown to be more effective than placebo . A randomized controlled study of metoklorpromid for central hiccups, including patients with brain tumors, likewise found this commonly used anti-nausea drug more effective than placebo.

Another drug for central hiccups is gabapentin, with several case studies suggesting benefit. Its effect on peripheral hiccups is proposed to be limited. This medication is used for neuropathic pain that can result from cancer or its treatments.

Dexamethasone, a cortisone-containing drug, is used for nausea and vomiting. However, it can cause intractable hiccups. Patients with dexamethasone-induced hiccups may benefit from alternating it with another cortisone drug, methylprednisolone.

Nonpharmacological (Non-Drug) Hiccup Treatments

Interventional procedures are also used in addition to medications. Cases trying these are few. The procedures block or stimulate the nerves involved in hiccup generation and responsible for diaphragm stimulation (phrenic and vagus nerves). Few clinicians have expertise, so benefits and harms must be carefully assessed. They may be options for intractable hiccups seriously affecting quality of life and unresponsive to all other possible treatments.

Among complementary medicine methods, acupuncture studies for hiccups suggest it may be beneficial when added to medication.

In conclusion, hiccups in cancer

• may result from the tumor itself, cancer treatment or the other causes listed above,
• are a common side effect affecting up to 10% of cancer patients, and
• can be treated with appropriate approaches.