Hiccups Treatment & Management

Generations of physicians have failed to discover a definitive cure for hiccups. The following statement from the Mayo Clinic, though made in 1932, still describes the situation perfectly: "The amount of knowledge on any subject such as this can be considered as being in inverse proportion to the number of different treatments suggested and tried for it."

Patients rarely present to the emergency department (ED) after cessation of a brief episode of hiccups. If this occurs, the possibility of another reason for the presentation (eg, depression) should be considered first.

Supportive care is administered as indicated by the causative pathology (eg, oxygen for the patient whose hiccups may be secondary to pneumonia). Therapy is directed first toward at the cause of the hiccups (if identified) and then toward the hiccups themselves (if necessary).

Gastroesophageal reflux is associated closely with hiccups but may be either a cause or an effect. Acid perfusion studies should be done to confirm the inducibility of hiccups before antireflux surgery is performed to cure hiccups.

Treatment may be pharmacologic or nonpharmacologic. Chlorpromazine remains the only agent approved by the US Food and Drug Administration (FDA) for the treatment of intractable hiccups. ^{[2, 18]} Surgical phrenic nerve ablation has been advocated for intractable cases that are unresponsive to other treatment. This drastic approach may be associated with considerable morbidity and is not universally successful. A Cochrane review concluded that the available evidence was insufficient to guide treatment of persistent or intractable hiccups by either pharmacologic or nonpharmacologic means. ^[19]

Consultation is rarely necessary unless the cause of the hiccups calls for the participation of a specialist.

Various agents have been reported to cure hiccups. Gabapentin, baclofen, and metoclopramide appear to show promise for persistent hiccups alone, in combination with other drugs, including proton-pump inhibitors, or as conjoined therapy. ^{[2, 18]}  In a systematic review of pharmacologic therapy for persistent/intractable hiccups in 341 patients in 15 studies, Steger et al noted that treatment of the underlying condition was the most successful, but there were no high-quality data to allow pharmacologic treatment recommendations. ^[20] However, on the basis of the limited data available, the investigators indicated that owing to their lower risk of adverse effects over long-term therapy as compared with traditional neuroleptic agents, baclofen and gabapentin may be considered first-line therapy for persistent/intractable hiccups, with metoclopramide and chlorpromazine in reserve.

Chlorpromazine is the most thoroughly studied medication, is FDA-approved for intractable hiccups, and appears to be the drug of choice in many reports. Regimens in the range of 25-50 mg intravenously (IV) or intramuscularly (IM) are effective in 80% of cases. To prevent or minimize hypotension caused by this agent, preloading the patient with 500-1000 mL of IV fluid is advised.

Another major tranquilizer, haloperidol, is effective in doses of 2-5 mg. Metoclopramide has been used successfully in a dosage of 10 mg every 8 hours. Indeed, a double-blind, randomized, controlled pilot study by Wang and Wang provided evidence of the usefulness of metoclopramide against intractable hiccups. ^[1] In this study, 34 patients received either 10 mg of metoclopramide or placebo three times per day for 15 days. The efficacy of metoclopramide with regard to cessation or improvement of hiccups was greater in the metoclopramide group than in the placebo group; no serious adverse effects were noted.

Several anticonvulsant agents have been used to treat intractable hiccups. Phenytoin, valproic acid, and carbamazepine have all been effective when used in typical anticonvulsant doses. Gabapentin has been shown to be effective in patients with central nervous system (CNS) lesions and in some other etiologic groups. ^{[21, 22, 23]}

Of the anesthetic agents, ketamine has been the most successful in a dose of 0.4 mg/kg (one fifth of the usual anesthetic dose). The centrally acting muscle relaxant baclofen, ^[24] in a dosage of 10 mg orally every 6 hours, is particularly useful in patients for whom other agents are contraindicated (eg, those with renal impairment). A case report described success with oral baclofen for persistent hiccups occurring after an epidural steroid injection. ^[25] Another case report has described the combination of baclofen and low-dose olanzapine. ^[26] IV lidocaine, in a loading dose of 1 mg/kg followed by an infusion of 2 mg/min, has cured patients after other agents were unsuccessful. Oral lidocaine was reported to be successful in four cancer patients with hiccups. ^[27]

Other agents reported to be beneficial are as follows:

• Muscle relaxants
• Sedatives
• Analgesics (eg, orphenadrine, amitriptyline, chloral hydrate, and morphine)
• Stimulants (eg, ephedrine, methylphenidate, amphetamine, and nikethamide)
• Miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, ^[12] and nifedipine)

A randomized, single-blind, crossover phase III trial of 65 cancer patients treated with chemotherapy who had dexamethasone-induced hiccup found that rotation of the antiemetic corticosteroid from dexamethasone to methylprednisolone significantly reduced hiccup intensity, without a change in emesis intensity, compared to that when dexamethasone was maintained. ^[28] When dexamethasone was readministered instead of methyprednisolone at the crossover phase, the hiccup intensity increased again. Note: All 65 patients were female, although the investigators did not exclude female patients in the enrollment process.

Benzodiazepines exacerbate or precipitate hiccups and should be avoided. ^[15]

Many of the traditional nonpharmacologic remedies used in the emergency department have a sound physiologic basis, in that they have an effect on components of the hiccup reflex. The following are examples:

• Stimulation of the nasopharynx by applying forcible traction to the tongue, swallowing granulated sugar, gargling with water, sipping ice water, drinking from the far side of a glass, biting on a lemon, or inhaling noxious agents (eg, ammonia)
• C3-5 dermatome stimulation by tapping or rubbing the back of the neck, coolant sprays, or acupuncture
• Direct pharyngeal stimulation by a nasal or oral catheter (90% effective)
• Direct uvular stimulation by a spoon or cotton-tip applicator
• Removal of gastric contents by means of emetics or a nasogastric tube

The following remedies lead to vagal stimulation (only one should be used at any given time):

• Iced gastric lavage
• Valsalva maneuver
• Carotid sinus massage (performed only by experienced personnel after exclusion of contraindications)
• Digital ocular globe pressure (performed only by experienced personnel after exclusion of contraindications)
• Digital rectal massage

Various techniques are used that interfere with normal respiratory function, such as the following:

• Breath holding
• Hyperventilation
• Gasping (as in fright)
• Breathing into a paper bag (which increases arterial carbon dioxide tension [PaCO ₂])
• Pulling the knees up to the chest and leaning forward
• Using continuous positive airway pressure
• Rebreathing 5% carbon dioxide

Mental distraction sometimes works. For example, the patient may be asked to "think of a loved one remembering you." An inventive naval doctor achieved success by offering $10 if the patient could continue to hiccup immediately.

The following nonpharmacologic approaches have also been tried:

• Behavioral conditioning (including other members of the family unit)
• Hypnosis
• Acupuncture (including near-infrared irradiation of acupoints) ^{[29, 30, 31, 32]}
• Phrenic nerve or diaphragmatic pacing – Incidental cure of hiccups during cardioversion has been reported
• Prayer - One patient, after 8 years of hiccupping and more than 60,000 suggested treatments, finally obtained relief after praying to St Jude, the Catholic patron saint of lost causes

The final and most drastic treatment for hiccups is phrenic nerve ablation. Fluoroscopic examination may reveal unilateral involvement, which allows directed therapy. Initially, temporary blockade is advisable. Bilateral phrenic nerve interruption may lead to significant respiratory complications and may not always cure hiccups, because other respiratory muscles are involved. All other treatments must be explored before this step is embarked on.

Microvascular decompression of the vagus nerve has been reported to be successful in case reports. ^{[33, 34]}