Evaluation and Management of Coughs and Hiccups
Evaluation and Management of Coughs and Hiccups
Authors:
Samuel H.F. Lam, MD, RDMS, FACEP, Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, IL.
Conal Roche, MD, Department of Emergency Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL.
Peer Reviewer:
John Sarko, MD, Maricopa Medical Center, Assistant Professor, Emergency Medicine, University of Arizona–Phoenix Medical School, Phoenix, AZ.
Coughs and hiccups are common emergency department complaints. While the majority of their causes are benign, patients with these symptoms can suffer from significant distress and impaired quality of life. Most patients with these symptoms can be effectively managed by understanding the pathophysiology and differential diagnosis of these symptoms and by using evidence-based therapy. It is important for the physician to be aware of the emergent conditions that may present with these seemingly benign complaints.
Cough
Cough is one of the most common chief complaints in the emergency department.1-3 Cough is categorized as acute if it lasts less than three weeks, subacute if it lasts three to eight weeks, and chronic if it lasts more than eight weeks. Most coughing episodes are acute, but in nonsmokers, there is about a 12-14% incidence of cough lasting longer than three weeks, and the incidence of chronic cough is about 1%.4 Illnesses that produce cough impair the quality of life and are responsible for over 20 million lost days of work in the United States each year.5-6
Pathophysiology
A cough may be either a pure reflex or a volitional response. Laryngeal, or reflex cough, is often triggered by aspiration, with minimal associated inspiration. Tracheobronchial cough is initiated by receptors distal to the larynx and may occur voluntarily or by a reflex arc. Coughing is obviously protective, preventing aspiration and enhancing ciliary action and debris clearance.
Afferent receptors for the "cough pathway" are located throughout the upper and larger airways. Afferent arcs are mediated by the vagus nerve. In the proximal airways, the afferent receptors are predominantly mechanoreceptors that shift primarily to chemoreceptors in the distal airways. In some individuals with variant vagus nerve innervation to the tympanic membrane, cough response can be triggered by stimulation to the external ear canal. The central and brainstem cough centers are subject to extensive and poorly understood modulation from other respiratory reflex arcs, sleep state, and voluntary initiation and suppression. The efferent pathway initiates laryngeal and respiratory muscles, as well as reflexive pelvic sphincters.
Causes of cough are often divided into upper and lower airway sources, but research has shown similarly elevated levels of inflammatory markers in the lower airways in most conditions, leading to a more unified airway theory.7
Pathologic states that potentially result in chronic cough may work by increased airway receptor exposure to stimulating tachykinins, upregulation or sensitization of receptors, or by central modulation of the reflex arc. More recently in the pulmonary literature, it has been suggested that, rather than fitting chronic cough into established diseases, it should be defined as a separate diagnosis of cough hypersensitivity syndrome.8
Etiology and Differential Diagnosis
Cough as the Chief Complaint in Life-threatening Diagnoses. Coughs are typically found in patients with tracheobronchial infections, such as pneumonia, bronchial inflammation, and chronic obstructive pulmonary disease (COPD) exacerbations. A potentially life-threatening condition, pulmonary embolism (PE) is an established mimic of community-acquired pneumonia.9,10 Cough was also identified as an independent predictor of delay in diagnosis of PE in emergency department patients.11 In a large 2008 retrospective review, cough was present in 12-43% of elderly patients with PE.12 In addition, PE has been shown repeatedly to be present in at least 20% of patients with atypical presentations of COPD exacerbation.13 Therefore, the presence of cough and even sputum production does not rule out the diagnosis of PE, especially in an older population.10 This same level of caution should apply to patients known to have increased risk for thromboembolic disease when cough is not explained by infectious or post-infectious causes.14
Experienced clinicians are aware that cough can be associated with heart failure (HF).15 In patients who present with persistent non-productive cough, HF should be considered in the context of suggestive findings on history and physical exam.
Significant correlation has been found between chronic cough and myocardial infarction (MI).16 In another study, 15% of patients who subsequently were found to have anterior MI complained of cough in addition to their chest pain. Patients with inferior and lateral MI were significantly less likely to have cough (3-6% incidence).17 Cough is also commonly seen with development of cardiac shock and pulmonary edema in the infarcting patient.
Acute Cough. Acute cough is commonly caused by upper respiratory tract infection (sinusitis, rhinitis, pharyngitis, laryngitis), lower respiratory tract infections (bronchitis, pneumonia), pertussis, allergic reactions, chemical or toxic exposure, as well as exacerbation of chronic conditions such as asthma, COPD, or interstitial lung disease.
Subacute Cough. Subacute cough is most commonly attributed to postinfectious etiology. Post-infectious cough is thought to be due to excessive inflammatory and hypersecretory changes to the upper and lower airways, along with cough receptor hypersensitivity after a viral infection.18
Chronic Cough. In a nonsmoking, immunocompetent patient with chronic cough, with no apparent infectious etiology, and not taking angiotensin-converting enzyme inhibitors (ACEI), greater than 90% will be attributed to upper airway cough syndrome, asthma, or gastroesophageal reflux disease, in this order of prevalence.2,19,20 Many patients have more than one process involved, further complicating evaluation.
Table 1: Conditions Encompassed by Upper Airway Cough Syndrome (UACS)
- Post-nasal drip syndrome
- Acute bacterial sinusitis
- Allergic fungal sinusitis
- Allergic rhinitis
- Nonallergic rhinitis with eosinophilia (NARES)
- Occupational rhinitis
- Postinfectious rhinitis
- Rhinitis due to anatomic abnormalities
- Rhinitis due to physical or chemical irritants
- Rhinitis medicamentosa (rebound rhinitis after use of nasal decongestants)
- Rhinitis of pregnancy
- Vasomotor rhinitis
Upper Airway Cough Syndrome (UACS). UACS is the most common cause of chronic cough and is implicated in up to 85% of chronic cough in nonsmokers.20,21 The diagnosis encompasses post-nasal drip syndrome and other common causes of rhinitis. (See Table 1.) The most commonly proposed mechanism involves draining nasal or sinus secretions into the hypopharynx and larynx causing recurrent irritation and stimulation of cough receptors.22 There is also evidence that patients diagnosed with UACS have a hypersensitive cough reflex.23 Patients with UACS typically present with a globus sensation, nasal secretions, or frequent throat clearing. However, absence of these symptoms does not necessarily exclude the diagnosis. Physical exam findings might include a visible draining trail of mucous or clear secretion in the posterior oropharynx, or cobblestoning and inflammation to the posterior pharyngeal mucosa.
Asthma and Non-Asthmatic Eosinophilic Bronchitis (NAEB). After UACS, asthma is the second most common cause of chronic cough in adults, affecting 24-29% of patients in the outpatient setting.24 Many of these patients will present with typical wheezing and asthma symptoms. In up to 57% of asthma cases, cough may be the only presenting complaint.25,26 This cough-variant asthma may present without the expected physical exam finding of wheezing, but will invariably respond to inhaled bronchodilators.
Patients with NAEB have eosinophilic airway inflammation (like asthma) but (unlike asthma) lack airway hyperresponsiveness.27 Bronchodilator therapy is typically ineffective, but they do respond to treatment with oral and inhaled corticosteroids. Diagnosis of NAEB is more suitably left to specialists. Nevertheless, it can be appropriate to initiate empiric therapy with inhaled corticosteroids in the emergency department so that an assessment of effectiveness is possible when the patient sees the specialist after discharge.
Gastroesophageal Reflux Disease (GERD). GERD is commonly thought to cause cough by microaspiration. However, numerous studies have now demonstrated an esophageal-tracheobronchial initiation of the cough reflex, elicited by lowered pH in the distal esophagus.28
GERD has been considered a common cause of chronic cough, but recent literature suggests that this is rarely an isolated cause of chronic cough.29,30 Cough caused by reflux disease was believed to be present without classic reflux symptoms up to 75% of the time.30 This was largely derived from a study of coughing patients who were questioned about typical GERD symptoms after empiric therapy for GERD led to improvement in cough.28 A Cochrane review in 2011 left significant doubt regarding the validity of this assumption, although significant improvement in cough scores was noted after two to three months of empiric therapy with proton pump inhibitors compared with placebo.31
Diagnostic Approach to the Coughing Patient
Acute Cough.32,33 (See Figure 1.) Evaluation of acute cough should focus on diagnosis of an upper or lower respiratory infection, an exacerbation of a chronic respiratory condition, environmental or ACEI exposure, and whether the presentation could represent atypical HF, acute coronary syndrome (ACS), or PE presentation.
Figure 1: Acute Cough
Acute bronchitis is one of the most common emergency department diagnoses provided for the coughing patient, but is thought to be overused.34 The diagnosis of acute bronchitis should only be considered in a patient with cough less than three weeks, in the absence of exacerbation of chronic reactive airway disease or nasal and upper respiratory tract symptoms more consistent with the common cold, and without evidence for pneumonia on chest radiography.34
Subacute Cough. Similar to acute cough evaluation, subacute cough assessment should focus on identifying post-infectious or ongoing infectious sources. Suspicion for pertussis and post-viral bacterial pneumonia should be higher in these patients. If no infectious source is apparent, these patients should be evaluated as chronic cough patients.
Chronic Cough.24,29,33,35 (See Figure 2.) Patients presenting with chronic cough should be asked about risk factors and symptoms that might suggest the presence of HIV/AIDS, tuberculosis, cancer, and any other immunocompromised status. It is appropriate to obtain a chest radiograph, primarily to assess for radiopaque foreign body, bronchogenic carcinoma, or mediastinal mass.
Figure 2: Chronic Cough
Environmental and Occupational Causes
Current data suggest that up to one in six cases of adult asthma and chronic cough can be attributed to occupational exposure.36,37 Along with questions about smoking and ACEI use, it is reasonable to screen patients with chronic cough for occupational exposures. Questions about co-workers with similar symptoms, whether there is improvement of complaints on the weekend or vacation, or if the patient can recall a sentinel event (spill, explosion), are all appropriate in the evaluation.
At-risk groups include mine workers, farmers, painters, cleaners, bakers, and lumber industry workers, among others exposed to high levels of aerosolized substances.38 The most common agents found to contribute to occupational chronic cough and asthma symptoms are: adhesives, metals, resins, flour and grain dust, latex, animals, aldehydes, and wood dust.36 Farming is associated with numerous respiratory hazards and results most commonly in asthma and rhinitis. Exposure to wet winter conditions and high mold counts in stored crops can lead to fungal pneumonias and hypersensitivity syndromes. Several severe acute cough syndromes are also associated with high nitrite gas or organic dust exposure.39 Symptom monitoring of 9/11 World Trade Center responders suggests a 12-fold rate of chronic cough and bronchitis symptoms in exposed individuals.40
Patients should be informed of the risks of continued exposure to inciting toxins or triggers and referred to an occupational medicine or pulmonary clinic if available. Work restriction, personal protective measures, or appropriate trigger avoidance should be suggested.
Evaluation for Pertussis
The presence of prolonged cough and upper respiratory infectious symptoms should raise suspicion for pertussis. Studies have shown up to 20% of urban adult patients presenting for greater than two weeks of cough have positive pertussis antibody on testing.41,42 Paroxysmal cough, inspiratory whoop, or post-tussive emesis is less likely to be present in a previously vaccinated population.
Microbial culture has been the gold standard to diagnose pertussis, but may miss more than 50% of cases (sensitivity 12-60%), especially when symptoms have been present for two weeks or more. Polymerase chain reaction (PCR) is much more sensitive (70-99%), but may return up to 14% false positives. Direct fluorescent antibody (DFA) testing gives results within minutes, but has highly variable sensitivity and specificity, and is not recommended by the Centers for Disease Control and Prevention. In general, if the patient presents in the first three weeks of disease, nasopharyngeal swabs should be sent for PCR or DFA, depending on the individual lab, along with microbial culture. If the patient presents after three weeks, serologic testing may be more appropriate, as the nasopharyngeal swabs become even less sensitive at this point. However, if the clinician has high pre-test suspicion for pertussis based on the presence of classic symptoms or known exposure in an unvaccinated individual, treatment should be initiated regardless of testing results due to limited sensitivity in all of the available tests.43 Furthermore, these tests should not be used to screen patients in whom there is very low or no suspicion for pertussis, as this will result in high false-positive rates and unnecessary antibiotic use.
Patients should be isolated from unvaccinated or under-vaccinated individuals, especially infants, at least until 5-7 days of therapy are completed, but ideally for four weeks. Therapy will not decrease the duration of symptoms once patients have reached a paroxysmal cough stage, but will decrease the rate of transmission.43
Management of Chronic Cough
ACEI Use and Smoking. Studies have shown that cough is present in up to 10-12% of patients taking ACEIs. Patients with chronic cough and ACEI use for less than one year should have them discontinued, preferably in conjunction with their primary physicians.33,44 ACEI-induced cough should be expected to resolve from two days to two weeks after cessation, but may take as long as four weeks to see improvement.44
Smokers should be offered counseling for quitting and should expect improvement in coughing within four weeks after smoking cessation.33
Table 2: Treatment Choices for Undifferentiated Chronic Cough
|
Condition |
Medication |
Dosage |
|
UACS |
First-generation antihistamines |
Chlorpheniramine 4 mg PO every 4-6 hours, diphenhydramine 25- 50 mg PO every 4-6 hours |
|
Decongestant |
Pseudoephedrine 60 mg PO every 4-6 hours |
|
|
Asthma |
B2-agonist inhaler |
Albuterol MDI 2 puffs as needed |
|
Steroid inhaler |
Beclomethasone MDI 2 sprays (80 mcg/spray) once daily |
|
|
GERD |
Behavioral modification |
Avoid common dietary triggers, large meals, meals before bed |
|
Proton pump inhibitor |
Omeprazole 40 mg PO once daily |
|
|
Prokinetic agent |
Metoclopramide 10 mg PO 3 times a day |
UACS, Asthma, and GERD. (See Table 2.) Studies have shown that patients' descriptions of duration of symptoms, quality of cough, and sputum production are unreliable in establishing an eventual diagnosis.45 Therefore, these conditions are now defined by a response to therapy, rather than a classic constellation of symptoms. If one diagnosis appears most likely based on brief questioning, it is appropriate to treat this etiology first. Otherwise, therapy should be directed to each cause in order of prevalence.
UACS. In the undifferentiated patient, initial treatment should be directed at this potential cause. Therapy should involve a combination of a first-generation antihistamine and a decongestant.46 A minimum of two weeks' therapy is recommended, although complete symptom resolution might not be seen for several weeks or months.33
Asthma. In a patient who has failed a trial of antihistamines and a decongestant, it is appropriate to initiate a trial of inhaled albuterol in the emergency department, even in the absence of wheeze or prolonged expiratory respiration on exam. If the patient has improvement of symptoms, he or she may be discharged with an inhaled beta-agonist and inhaled corticosteroids with the presumptive diagnosis of cough-variant asthma and a referral back to the primary care physician or a specialist for follow-up and more extensive testing as needed.24,26 Even with normal spirometry and hyperresponsiveness testing, current recommendations allow for exclusion of cough-variant asthma as a source of chronic cough only after a trial of typical therapy has failed.26
GERD. Empiric treatment in the absence of typical GERD symptoms should not be instituted unless the patient has already failed an adequate trial of therapy for UACS and asthma. It is reasonable to suggest common lifestyle modifications that have been shown to improve reflux symptoms, while initiating therapy for UACS or asthma.30 If medical therapy is initiated from the emergency department, a proton pump inhibitor with or without a prokinetic agent is preferred.30,47,48 Treatment of up to 2-3 months might be necessary for effectiveness to be seen and responsiveness determined. However, the benefit of such an approach has been called into question by two recent publications.49,50
Role for Antibiotics in the Coughing Patient
Evidence supports antibiotic treatment for pneumonia, COPD exacerbation, and pertussis infections. (See Table 3.) Severe cases of acute sinusitis and sinusitis with symptoms lasting longer than a week may be assumed to be bacterial, and antibiotic therapy is often recommended. Severe sinusitis is characterized by high fever, exquisite tenderness to palpation of sinuses, or overlying cellulitis, in addition to the usual symptoms of nasal discharge, congestion, and sinus pain. Most other cases of sinusitis are due to viral sources that will likely resolve without antibiotic therapy.51
Table 3: Conditions Where Evidence Supports Antibiotics in the Coughing Patient46
|
Evidence for Antibiotics Use |
No Improved Outcomes with Antibiotics |
|
|
Acute bronchitis is a common diagnosis in the emergency department and is often associated with antibiotic prescription, contrary to recommendations of published guidelines.34,52,53 In a 2012 study, 74% of emergency department patients with a diagnosis of acute bronchitis were prescribed antibiotics, 77% of those being broad spectrum.54
Physicians were more likely to prescribe antibiotics if they thought the patient was expecting them. The practice of delayed antibiotic prescription has been suggested as a way to decrease unnecessary antibiotic use while preserving satisfaction scores. A Cochrane review in 2010 determined that there was little evidence to suggest improved patient satisfaction with delayed antibiotic prescribing compared with having the difficult conversation up front.55
Role for Cough Suppressants
Despite their widespread use, studies on the effectiveness of various cough suppressants are surprisingly scant and often contradictory. (See Table 4.) A recent Cochrane review found no good evidence for or against the effectiveness of over-the-counter remedies in adults with acute cough.56
Table 4: Choosing Suppressive Therapy63
|
Medication |
Acute cough/URI |
Subacute/chronic cough |
|
*small sample (i.e., N ≤ 15) |
||
|
Dextromethorphan |
Mixed, suggest benefit |
Benefit in chronic bronchitis/COPD* |
|
Codeine |
Mixed, suggest no benefit |
Mixed, suggest benefit |
|
Guaifenesin |
Mixed, suggest benefit |
Mixed, suggest benefit |
|
Inhaled ipratropium bromide |
Benefit in URI |
Benefit in COPD |
Opioids are believed to suppress cough via their action on the central nervous system. Codeine is a commonly prescribed drug in this class, yet evidence on its effectiveness is limited at best.57-60 Hydrocodone is recommended for cancer-related cough, but its use in cough of other etiologies is mostly inferred. Dextromethorphan has a more favorable side-effect profile, although clinical studies have yielded mixed results. More recently, slow-release morphine was found to be effective in patients with chronic cough in a double-blind, crossover, placebo-controlled trial.61
In terms of peripherally acting medications, inhaled ipratropium seems to be useful in suppressing acute and chronic cough in small studies. Guaifenesin has also been found to be generally effective. In a recent study, the addition of benzonatate to guaifenesin in patients with viral cough resulted in improved cough suppression, the first new evidence on its effectiveness in more than half a century.62
Disposition
Patients with cough may be discharged home from the emergency department if no serious or life-threatening pathology is found. Further outpatient workup, if indicated, should be coordinated with the patients' primary physicians or referral specialists.
Hiccups
A hiccup, also known as a hiccough or singultus, is due to sudden inspiration followed by abrupt closure of the glottis (Latin singult = a gasp or a sob). Hiccups are more common in children than adults, more common in adult men than in women, and more common in those with co-morbid conditions.64,65 While hiccups are often benign and self-limiting in most individuals, they can be debilitating and cause significant distress if prolonged. Hiccups are termed bouts if they last for less than 48 hours, persistent if they last for more than 48 hours, and intractable if they last for more than a month.
Pathophysiology
Hiccups are caused by involuntary, rhythmic contractions of the diaphragm and other accessory respiratory muscles. Their function is unknown, and the exact neurological pathway has yet to be elucidated. Nevertheless, they were thought to be mediated by a reflex arc with involvement of the central nervous system, the vagus nerve, and the phrenic nerve. A "hiccup center" is postulated to be located in the brainstem or the spinal cord, receiving afferent input from the vagus nerve, the phrenic nerve, and the sympathetic chain. Efferent outputs are transmitted mostly via the phrenic nerve. Multiple neuroreceptors (dopamine, serotonin, opioid, gamma-aminobutyric acid [GABA], and calcium channels) are hypothesized to be involved. Stimulation or pathology anywhere along the reflex arc can result in hiccups.
Etiology and Differential Diagnosis
Gastric distension from food, carbonated beverage, or aerophagia is a common cause of benign, self-limiting hiccups. Persistent hiccups are usually due to injury or irritation to the central nervous system, the vagus nerve, or the phrenic nerve. Since the vagus and phrenic nerves innervate or course near multiple head, neck, thoracic, and abdominal organs and structures, the differential diagnosis can be extensive. In addition, hiccups can be psychogenic, metabolic, or pharmacologic in etiology. (See Table 5.)
Table 5: Etiology of Hiccups
Central Nervous System Disorders
Ischemic/ hemorrhagic stroke
Arteriovenous malformation
Temporal arteritis
Encephalitis
Meningitis
Brain abscess
Neurosyphilis
Intracranial neoplasms
Brainstem neoplasms
Multiple sclerosis
Hydrocephalus
Syringomyelia
Head trauma
Cardiovascular Disorders
Myocardial infarction
Pericarditis
Abdominal aortic aneurysm
Gastrointestinal Disorders
Aerophagia
Gastric distension
Esophageal distension
Esophagitis
Gastritis
Hepatitis
Inflammatory bowel disease
Pancreatitis
Peptic ulcer disease
Pancreatic cancer
Gastric carcinoma
Abdominal abscess
Gallbladder disease
Peritonitis
Medications
Alpha methyldopa
Steroids
Benzodiazepines
Short-acting barbiturates
Chemotherapy agents
Post-operative
Gastric distension
General anesthesia
Intubation (stimulation of glottis)
Neck extension (stretching of phrenic nerve roots)
Traction on viscera
Psychogenic
Stress
Excitement
Conversion reaction
Malingering
Thoracic Disorders
Empyema
Pneumonia
Pleuritis
Asthma
Bronchitis
Aortic aneurysm
Mediastinitis
Chest trauma
Mediastinal and lung tumors
Thoracic adenopathy secondary to infection/neoplasm
Toxic-metabolic
Alcohol
Uremia
Hyperglycemia
Hyponatremia
Hypocalcemia
Hypocapnia
Vagus and Phrenic Nerve Irritation
Goiter
Pharyngitis
Laryngitis
Foreign body irritation of tympanic membrane
Neck cyst or tumor
Adapted from: Lembo AJ. Overview of hiccups. UptoDate. www.uptodate.com. Accessed 4/7/2012.
Diagnostic Approach in the Emergency Department
Patients with hiccups should be asked about onset, severity, and duration of symptoms, modifying factors, recent trauma or surgery, co-morbid conditions, alcohol and illicit drug use, and current medications. A concise review of systems may help uncover unsuspected causes. Associated neurologic, cardiac, respiratory, and gastrointestinal symptoms should be specifically sought. In general, hiccups that persist during sleep suggest an organic cause, while hiccups that resolve during sleep suggest a psychogenic cause, although this distinction is not absolute.
A careful physical examination should be performed in search of an underlying etiology. In particular, one should look for signs of potentially life-threatening conditions such as central nervous system pathology, myocardial injury, vascular dissection, acute surgical abdomen, and malignancy. The head and neck should be examined carefully to look for signs of trauma, infection, goiter, and other masses. An otoscopic exam should be diligently performed, since a rare but easily treatable cause of hiccups is a foreign body (usually hair) on the tympanic membrane stimulating the auricular branch of the vagus nerve.
An electrolyte and renal function panel can detect causes such as uremia, hypocalcemia, and hyponatremia. (See Figure 3.) Chest radiography may help identify intrathoracic pathology. A screening electrocardiogram (ECG) is prudent in patients with risk factors or significant co-morbidities for ischemic heart disease, since there have been case reports of hiccups as a presenting symptom in patients with myocardial infarction66 or ischemia.67,68
Figure 3: Diagnostic Approach to Hiccups in the Emergency Department
Management
Specific reversible causes should be treated when found. The following pertains to management of idiopathic or unrelenting cases of hiccups.
Many of the non-pharmacologic treatments suggested by various authors are based on stimulation of the vagus nerve or disruption of the normal respiratory cycle in the hope of interrupting the hiccough reflex arc. (See Table 6.) However, most of them have not been tested by rigorous scientific trials, and no one method seems to be more effective than others.
Table 6: Non-pharmacolog Treatment Options for Persistent or Intractable Hiccups
- Biting on lemon
- Breath-holding/breathing into paper bag
- Direct stimulation of nasopharynx or uvula with cotton swab/catheter
- Drinking from the opposite side of the glass
- Fright
- Ice water gargle
- Noxious odors (inhaling ammonia)
- Pulling knee to chest
- Swallowing granulated sugar/peanut butter
- Tongue traction
- Vagal maneuver (Valsalva, pressing on eyeballs, carotid sinus massage)
A myriad of pharmacologic agents have been reported to be effective in treatment of hiccups, lending support to the theory that multiple neuroreceptor types are involved in the postulated hiccough reflex arc. Chlorpromazine, a phenothiazine antipsychotic, is the only medication approved by U.S. Food and Drug Administration (FDA) for treatment of hiccups based on small case series. It is postulated to work by antagonism of central dopamine neuroreceptors. Haloperidol (non-FDA approved) likely has a similar mechanism of action.
Other off-label drugs reported to be effective hiccough treatment in case series consisting of more than 10 patients include gabapentin, baclofen, and metoclopramide.69-72 Valproic acid and nifedipine were also used to treat hiccough with some success in case series of five and seven patients, respectively.73,74 In addition, there have been numerous case reports attesting to successful hiccough therapy with various classes of medications such as anticonvulsants (phenytoin, carbamazepine), antidepressants (amitriptyline, sertraline), central nervous system agents (methylphenidate, amantadine, olanzapine), steroids (dexamethasone), benzodiazepines (midazolam), and antiarrhythmics (quinidine, lidocaine). To date there has not been any published clinical trial comparing the effectiveness of different hiccough medications. Hence, the choice of pharmacologic therapy is somewhat empirical and clinician-dependent. Most drug treatments are prescribed for 7-10 days and may be discontinued upon cessation of symptoms. (See Table 7.) Potentially serious side effects include hypotension, arrhythmias, glaucoma, and delirium.
Table 7: Common Drug Treatment Options for Persistent or Intractable Hiccups
|
Drug Name |
Initial Dose |
Maintenance Dose |
|
Chlorpromazine (Thorazine®) |
25-50 mg IV/IM |
25-50 mg PO three to four times a day |
|
Baclofen (Lioresal®) |
10 mg PO |
10-20 mg PO three times a day |
|
Metoclopramide (Reglan®) |
10 mg IV/IM |
10-20 mg PO three to four times a day |
|
Haloperidol (Haldol®) |
2-5 mg IM |
1-4 mg PO three times a day |
|
Gabapentin (Neurontin®) |
100 mg PO |
100-400 mg PO three times a day |
|
Valproic acid (Depakote®) |
15 mg/kg PO |
15 mg/kg/day PO divided two to three times a day. Increase by 250 mg every 2 weeks until hiccough cease or side effects develop |
|
Nifedipine (Procardia®, Adalat®) |
10-20 mg PO |
10-20 mg PO three to four times a day |
For refractory or debilitating hiccups, more invasive treatment options such as phrenic nerve block, controlled phrenic and vagal nerve stimulation, and phrenic nerve crushing via surgery can be considered in consultation with the appropriate specialists. Alternative medicine treatments such as hypnosis and acupuncture have also been found to be effective in some cases.75-78
Disposition
Generally, patients with hiccups can be discharged home if no significant pathology is found during an emergency department screening examination.
In cases of failed non-pharmacologic treatment, medications such as chlorpromazine, haloperidol, metoclopramide, baclofen, among others, can be initiated. Well-appearing patients with negative emergency department screening examinations can be sent home on 7-10 days of outpatient therapy.
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Coughs and hiccups are common emergency department complaints. While the majority of their causes are benign, patients with these symptoms can suffer from significant distress and impaired quality of life. Most patients with these symptoms can be effectively managed by understanding the pathophysiology and differential diagnosis of these symptoms and by using evidence-based therapy. It is important for the physician to be aware of the emergent conditions that may present with these seemingly benign complaints.Subscribe Now for Access
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