Hiccups Treatment & Management

Ahmed Mohamed BadheebProf Of Oncology & Internal Medicine

Approach Considerations

• 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."

In the ER

• 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.

Therapy

• 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).

Pharmacologic Therapy

• Various agents have been reported to cure hiccups. • In a 2015 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. [17]

baclofen and gabapentin

• 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 and appears to be the drug of choice in many reports.

Chlorpromazine

• 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.

haloperidol

• Another major tranquilizer, haloperidol, is effective in doses of 2-5 mg.

Metoclopramide

• 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]

Metoclopramide

• 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.

Anticonvulsant agents

• 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

• Gabapentin has been shown to be effective in patients with central nervous system (CNS) lesions and in some other etiologic groups. [18, 19, 20]

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, [21] 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 has described the combination of baclofen and low-dose olanzapine. [22]

• baclofen 5mg po TID + Olanzapine 5mg OD=Zyprexa

• 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. [23]

Other agents• 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, [10] and nifedipine)

Benzodiazepines

• Benzodiazepines exacerbate or precipitate hiccups and should be avoided. [13]

Gastroesophageal reflux

• 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.

Surgical phrenic nerve ablation • 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.

Cochrane review

• A Cochrane review concluded that the available evidence was insufficient to guide treatment of persistent or intractable hiccups by either pharmacologic or nonpharmacologic means. [16]

Consultation

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

Chlorpromazine

• is the most thoroughly studied medication 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.

haloperidol

• 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] .

metoclopramide

• 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. [18, 19, 20]

Anesthetic agents• ketamine has been the most successful in a

dose of 0.4 mg/kg (one fifth of the usual anesthetic dose).

Anesthetic agents• The centrally acting muscle relaxant

baclofen, [21] 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).

Combination of baclofen and low-dose olanzapine.

• A case report has described the combination of baclofen and low-dose olanzapine. [22]

IV lidocaine

• 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• Oral lidocaine was reported to be successful in four cancer patients with hiccups. [23]

• Neuhaus T, Ko YD, Stier S. Successful treatment of intractable hiccups by oral application of lidocaine. Support Care Cancer. 2012 Nov. 20(11):3009-11. [Medline].

• Life-threatening and fatal events in infants and young childrenPost marketing cases of seizures, cardiopulmonary arrest, and death in patients under the age of 3 years have been reported with use of lidocaine hydrochloride oral topical solution 2% (viscous) when it was not administered in strict adherence to the dosing and administration recommendations. In the setting of teething pain, lidocaine hydrochloride oral topical solution 2% (viscous) should generally not be used. For other conditions, the use of the product in patients less than 3 years of age should be limited to those situations where safer alternatives are not available or have been tried but failed.

Successful treatment of intractable hiccups by oral application of lidocaine.

• Support Care Cancer.  2012; 20(11):3009-11 (ISSN: 1433-7339)• Neuhaus T; Ko YD; Stier S

• BACKGROUND: Persistent and intractable hiccups are a rather rare, but distressing gastrointestinal symptom found in palliative care patients. Although several recommendations for treatment are given, hiccups often persist.

• CASE REPORTS: We describe a new pharmacological approach for successfully treating hiccups in four cancer patients. In the first patient, chronic and intractable hiccups lasted for more than 18 months, but disappeared immediately after swallowing a viscous 2 % lidocaine solution for treatment of mucositis. Based on this experience, we successfully treated three further patients suffering from singultus using a lidocaine-containing gel. To our knowledge, this is the first report about managing hiccups by oral application of a lidocaine solution.

Lidocaine Topical Oral Solution Dosage and AdministrationAdult:

• The maximum recommended single dose of lidocaine hydrochloride oral topical solution, 2% (viscous) for healthy adults should be such that the dose of lidocaine HCl does not exceed 4.5 mg/kg or 2 mg/lb body weight and does not in any case exceed a total of 300 mg.

• For symptomatic treatment of irritated or inflamed mucous membranes of the mouth and pharynx, the usual adult dose is one 15 mL tablespoonful undiluted. For use in the mouth, the solution should be swished around in the mouth and spit out. For use in the pharynx, the undiluted solution should be gargled and may be swallowed. This dose should not be administered at intervals of less than three hours, and not more than eight doses should be given in a 24-hour period.

Nonpharmacologic Therapy

• Many of the traditional nonpharmacologic remedies used in the ED 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

Nonpharmacologic Therapy

• 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)

Nonpharmacologic Therapy

• 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

Nonpharmacologic Therapy

• 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.

Nonpharmacologic Therapy• Behavioral conditioning (including other members of the

family unit)• Hypnosis• Acupuncture (including near-infrared irradiation of

acupoints) [24, 25, 26, 27]

• 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

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, [10] and nifedipine)• Benzodiazepines exacerbate or precipitate hiccups and should be

avoided. [13]

Surgical Intervention

• 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. [28, 29]

Medication Summary

• Various agents have been reported to cure hiccups. Chlorpromazine appears to be the drug of choice. Haloperidol and metoclopramide have been used successfully. Several anticonvulsant agents (eg, phenytoin, valproic acid, and carbamazepine) have effectively treated intractable hiccups in typical anticonvulsant doses. Gabapentin has been effective in patients with central nervous system (CNS) lesions and in some other groups.

• Of the anesthetic agents, ketamine has been the most successful. Baclofen is particularly useful in patients for whom other agents are contraindicated. Lidocaine has cured patients after other agents were unsuccessful. Other reportedly beneficial agents include muscle relaxants, sedatives, analgesics, stimulants, and various miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, and nifedipine). Benzodiazepines should be avoided.

Diagnosis and management of hiccups in the patient with advanced cancer.

J Support Oncol. 2009 Jul-Aug;7(4):122-7, 130.Diagnosis and management of hiccups in the patient with advanced cancer.Marinella MA1.Author information1Department of Internal Medicine, Wright State University School of Medicine, Dayton, Ohio, USA. Mmarinella@pol.netAbstract

Benign, self-limited hiccups are more of a nuisance, but persistent and intractable hiccups lasting more than 48 hours and 1 month, respectively, are a source of significant morbidity in the patient with advanced malignancy.The hiccup reflex is complex, but stimulation of vagal afferents followed by activation of efferent phrenic and intercostal nerve pathways results in contraction of the diaphragm and intercostal muscles, respectively.The etiology of hiccups in the cancer and palliative care population may include chemotherapy, electrolyte derangements, esophagitis, and neoplastic involvement of the central nervous system (CNS), thorax, and abdominal cavity. Prolonged hiccups can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. Evaluation should be symptom-directed, focusing mainly upon the CNS and thoracoabdominal cavities as well as assessment of medications and serum chemistries. Most patients with ongoing hiccups require pharmacotherapy, with chlorpromazine being the only US Food and Drug Administration-approved agent. However, numerous other medications have been reported to be efficacious for treating intractable hiccups. Gabapentin has recently been shown to terminate hiccups effecitvely in cancer patients and may emerge as a therapy of choice in the palliative setting due to favorable tolerability, pain-modulating effects, minimal adverse events, and lack of drug interactions.

Management of intractable hiccups: an illustrative case and review.

Am J Hosp Palliat Care. 2014 Mar;31(2):220-4. doi: 10.1177/1049909113476916. Epub 2013 Feb 12.

Management of intractable hiccups: an illustrative case and review.Rizzo C1, Vitale C, Montagnini M.Author informationAbstractOften thought of as a benign and self-limited condition, hiccups can become persistent or

intractable, and thus be associated with substantial morbidity and distress. In such cases, an underlying etiology is often present, and may be overlooked. Debilitating hiccups can present a major challenge to optimal symptom management. Various causes of protracted hiccups have been identified including metabolic abnormalities, central nervous system pathology, malignancy, medications, and disorders attributed to cardiac, pulmonary and gastrointestinal etiologies. We present a case of intractable hiccups in a patient with an advanced hematological malignancy and review specific therapies for the management of persistent hiccups.

KEYWORDS:bone marrow transplantation; cancer; gabapentin; hiccups; olanzapine; palliative care

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