Nausea and Vomiting

by Leslie Hanna

As defined by Webster's dictionary, nausea is "stomach distress with distaste for food and an urge to vomit." Nausea is a distressing but frequently nonspecific symptom; its causes are often multifactorial and rarely straightforward. The subjective nature of the experience of nausea also makes it a complex subject and, ultimately, necessitates a thorough and individualized approach to its evaluation and treatment.

People with HIV/AIDS may experience nausea and vomiting at any stage of HIV infection, attributable to any of a number of various causes (discussed in the next section). Apart from the discomfort associated with nausea, moderate-to-severe nausea may compromise quality of life and prevent a person from carrying out activities of daily living. In addition, nausea is associated with loss of appetite and, if chronic, malnutrition and wasting, which is exacerbated by vomiting-related dehydration and nutrient depletion. Vomiting may cause damage to the esophagus (the tube involved in swallowing) or serious bleeding. Electrolyte (salt) imbalances that result from vomiting can cause heart and other muscle problems. Severe electrolyte abnormalities may be life-threatening.

For people with HIV, one of the most common adverse consequences of nausea and vomiting is a deterimental effect on adherence to prescribed oral drug regimens (e.g., protease inhibitors, drugs taken to prevent Pneumocystis carinii pneumonia [PCP]). For the sake of both palliative relief and optimal health for persons with HIV, acute or persistent nausea and vomiting merit prompt evaluation.

This article will provide information intended to help readers determine when to seek medical help for nausea and vomiting, as well as information about common causes and treatment options.

What Causes Nausea and Vomiting?

There are many potential causes of nausea and vomiting in the context of HIV disease. Although primary HIV infection is often asymptomatic, 30-50% of people experience an "acute retroviral syndrome" (ARS). ARS is a flu-like syndrome that follows infective HIV exposure and may involve lymphadenopathy (swollen lymph nodes), fever and headache, and sometimes nausea and rash. In early HIV infection, a person may experience a variety of constitutional (affecting the entire body) symptoms alone or in various combinations, including nausea, headache, fatigue, myalgia (muscle pain), fever and night sweats.

In late-stage HIV disease, constitutional symptoms may become more common, along with diarrhea and weight loss. These symptoms often result from an AIDS-defining condition such as gastrointestinal Mycobacterium avium complex (MAC), cytomegalovirus (CMV) disease or Kaposi's sarcoma, or from gastrointestinal Candida or cholangitis (bile duct inflammation). Brain conditions related to AIDS (e.g., cryptococcal meningitis) also can cause vomiting due to effects on the brain's vomiting center.

Nausea and vomiting that occur in response to something eaten, colloquially referred to as "food poisoning," are often accompanied by other symptoms such as diarrhea and abdominal cramping. Caused by ingesting food-borne bacteria, viruses or toxins, this type of gastrointestinal infection is fairly common in the general population and is usually transient. However, it may be life-threatening in a person with AIDS, particularly someone with late-stage disease. Bacterial infection may become chronic or recurrent, causing additional immune suppression, wasting and death.

Treatment is often aimed at reducing symptoms and, if possible, curing the infection, so prevention is critical. Proper food handling, preparation and care, along with other general hygienic precautions, are important aspects of a preventive strategy. See Food Safety Guidelines in this issue of BETA. The Food and Drug Administration (FDA) has published food and drug-related guidelines specifically for people with HIV/AIDS, and healthcare providers (doctors, nurses and registered dietitians) can also provide important preventive information about food handling and hygiene.

There are some general, non-HIV-related types or causes of nausea that may affect people with HIV from time to time, including nausea and vomiting that result from traveling in a car, boat or airplane (motion sickness), or that result from psychological or emotional upset. Triggers that occasionally provoke nausea in some people include certain sights, smells or tastes (e.g., the sight or smell of certain foods). Other conditions that occur in the general population can cause nausea and vomiting, including head injury, heart attack, hepatitis, dyspepsia (stomach upset), peptic ulcer disease, gastroesophageal reflux disease (stomach acid in the esophagus), pregnancy and use of alcohol or recreational drugs.

For people with HIV, nausea and vomiting are often side effects of medications or symptoms of an underlying illness. Other causes include metabolic or endocrine (glandular) disturbances and gastrointestinal mechanical or absorptive problems.

For HIV positive persons at any stage of HIV infection, persistent or severe nausea and vomiting should be evaluated and treated. Prompt and effective treatment that addresses the causes of debilitating nausea and vomiting is critical for optimal management of HIV disease.

Medications Used in HIV Disease Management May Cause Nausea and Vomiting

Many drugs commonly used in the treatment of HIV disease may cause nausea and vomiting in some patients. Nausea may interfere with taking important drugs that otherwise have great benefit. If medication is determined to be the cause of nausea, a physician or pharmacist can help a patient to devise an appropriate, individualized strategy that will successfully reduce or relieve medication side effects and ensure that beneficial medications can be taken. Later in this article, options will be outlined for people experiencing nausea and vomiting as side effects of medication.

The following classes of drugs have been reported to cause nausea and vomiting in at least 5% of people with HIV:

• antiretroviral agents, including the protease inhibitors ritonavir (Norvir), saquinavir (Invirase), indinavir (Crixivan) and nelfinavir (Viracept), and the nucleoside analogs AZT (Retrovir) and ddI (Videx)
• antiparasitic and antiprotozoal agents, including high-dose (as would be used for treating PCP, in contrast to lower doses used for prophylaxis) trimethoprim-sulfamethoxazole (TMP-SMX; Bactrim, Septra), atovaquone (Mepron) and clindamycin (Cleocin HCl)
• antimycobacterial agents (for tuberculosis and/or MAC) such as the macrolide drugs clarithromycin (Biaxin) and azithromycin (Zithromax), rifampin (Rifadin, Rimactane) and rifabutin (Mycobutin)
• antifungal agents, including fluconazole (Diflucan), ketoconazole (Nizoral) and itraconazole (Sporanox)
• pain medications, including codeine, hydrocodone (Vicodin), ibuprofen, oxycodone (Percocet or Percodan) and morphine.

Virtually all agents used for cancer chemotherapy may cause nausea and vomiting.

Whether an individual will experience nausea and vomiting when taking medications is also influenced by a host of factors including immune status, the use of other drugs and nutritional status.

Guidelines for Evaluating Nausea and Vomiting

The causes of nausea and vomiting determine the best treatment methods, as well as the best ways to prevent and/or manage chronic or recurrent symptoms. Contacting a doctor is recommended for anyone who is concerned about his/her own nausea and vomiting, and necessary in the event of any of the following:

• repeated episodes of vomiting over a 24-hour or longer period, without improvement
• the presence of blood or partially digested blood (which may resemble coffee grounds) in vomit
• additional symptoms such as dizziness, thirst, persistent fever, abdominal pain, jaundice (yellowing of the skin or whites of the eyes), diarrhea or severe headache
• inability to take necessary medications
• inability to urinate or absence of urination after 8-12 hours (adults).

Medical evaluation must encompass the entire spectrum of possible causes of nausea and vomiting. The physician will ask the patient to describe the severity and duration of the nausea, and whether or not there is any associated vomiting. The patient's health status (viral load, CD4 cell count, history of AIDS-defining illnesses, recent changes in status) will be considered to help determine whether or not the symptoms might be associated with a new, AIDS-defining illness. Other aspects for consideration include drugs(s) in current use, the presence or absence of other associated symptoms (e.g., diarrhea, fever, headache), and recent events such as travel, camping or dietary changes.

In addition to taking a history and examining the abdomen, the physician may order blood and urine tests to evaluate liver, kidney, pancreatic and gallbladder functions. Additional tests that may be useful include an upper GI series (x-ray examination of the stomach and gastrointestinal tract). Occasionally, stool tests are also ordered. Tests like ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) scans of the abdomen, and endoscopy (an internal examination of the gut or stomach using a long, flexible instrument for viewing) tend to be reserved for more complicated cases, which are more likely in people with advanced HIV disease.

Treatment generally begins after diagnosing the cause(s). However, antiemetic therapy designed to provide symptomatic relief of nausea and vomiting may begin before the ultimate diagnosis is made.

Guidelines for Treating Nausea and Vomiting

Treatment for nausea and vomiting primarily depends on the underlying cause(s), as well as on the severity of the symptoms. Simple interventions as well as "alternative" interventions, described in later sections of this article, may be most appropriate for persons who are experiencing mild, transient, self-limiting nausea and vomiting.

More severe symptoms or discomfort, or the presence of additional symptoms such as fever or bleeding, necessitate seeking a physician's evaluation and are likely to require treatment. There are many useful antiemetic drug treatments for nausea and vomiting that a physician may prescribe for patients. (See the chart of antiemetic agents, below, listed in descending order.)

If a medication is responsible for nausea and vomiting, consultation with a physician may identify approaches for relieving the symptoms. A review of all medications a person currently is taking is vital when evaluating nausea. It is helpful to bring all medications to doctor appointments, in order to review proper use and doses. Non-essential medications may be eliminated, and the dosages of other drugs may be adjusted. A drug desensitization regimen (in which a person begins with a reduced, tolerable dose of the drug and gradually builds up to the full dose) or switching to an alternate drug may also be appropriate. It is imperative to seek a physician's advice about altering any treatment regimen already in place.

If an underlying infection is identified as the cause of nausea and vomiting, treatment for that condition (e.g., antibiotics) should resolve the symptoms. Again, physicians often begin treatment for nausea and vomiting before a pathogenic organism has been identified, to bring relief of symptoms to the patient.

Standard Allopathic Drug Treatment

In some instances, such as when nausea and vomiting are severe or chronic, treatment with a type of drug called an antiemetic is necessary. Antiemetic drugs are designed to prevent or relieve nausea and vomiting. Each antiemetic has a mechanism of action that involves blocking certain brain receptors involved in stimulating the brain's so-called vomiting center, also known as the chemoreceptor trigger zone. Receptors include dopamine, histamine, serotonin and acetylcholine.

Antiemetics fall into several broad categories, based on mechanism of action. Antidopaminergics antagonize the action of the neurotransmitter dopamine; antihistamines inhibit histamine, a chemical that stimulates gastric secretion, constricts bronchial smooth muscle and dilates capillaries; and anticholinergics antagonize the action of the neurotransmitter acetylcholine.

Antidopaminergics include the phenothiazines (e.g., prochlorperazine) and the butyrophenones (e.g., haloperidol). Antihistamines act on diverse neural pathways and are considered most useful for treating symptoms related to motion sickness and vertigo (dizziness).

People with HIV/AIDS may have many different stimuli to the brain's vomiting center at the same time, so combinations of antiemetic drugs may be useful.

The chart below is a partial (i.e., not all-inclusive) listing of antiemetics that are commonly used in treating nausea and vomiting. Those agents ranked as first-line are those that are both cost-effective and capable of affecting a number of different stimuli, because they affect a number of different receptors. Agents in this category include diphenhydramine (Benadryl) and antidopaminergics such as proclorperazine (Compazine) and promethazine (Phenergan). They are considered useful for treating psychogenic as well as chemotherapy-induced nausea. First-line agents are used for acute bouts of nausea. Other agents that may be considered first-line may be used when dyspepsia or stomach upset is a concern, including antacids like Maalox or histamine blockers like cimetidine (Tagamet) or thimodidine (Pepsid AC). Because these agents may interact with anti-HIV drugs, it is essential to consult a doctor before using them, even those agents that are available over the counter.

Second-line agents include drugs that, like first-line agents, affect a range of stimuli but have increased specificity and potency for chronic nausea or chemotherapy-induced nausea.

Third-line agents are primarily serotonin antagonists. They are considered third-line primarily because of their high cost, and are used for refractory and chemotherapy-induced nausea.

In order to prevent recurrence of symptoms, antiemetic drugs may be given on a regular schedule, rather than as-needed. Oral administration is considered preferable, but antiemetics come in many forms including rectal suppositories and, for severe vomiting, injectable formulations.

Some experts have suggested adding low doses of haloperidol (Haldol) as adjunctive therapy to serotonin inhibitors.

Overall, the side effects of antiemetics tend to be more pronounced in older persons and in persons with advanced HIV disease, for whom lower doses may be effective. Mark Jacobs, PharmD, research pharmacologist at St. Francis Memorial Hospital in San Francisco, recommends "avoiding steroids in combination with antiemetics in people with HIV, with respect to their immunocompromise." Persons with HIV for whom he recommends pharmaceutical antiemetics -- particularly ondansetron -- include those taking amphotericin B for invasive fungal disease, chemotherapy for Kaposi's sarcoma or antivirals for CMV of the gastrointestinal tract.

Antiemetic agents commonly used in HIV disease management

(generic name, brand name and common side effects)

First-Line Agents

diphenhydramine (Benadryl): sedation, dry mouth, dizziness, urinary retention

lorazepam (Ativan): drowsiness, confusion, habit-forming

prochlorperazine (Compazine): drowsiness, involuntary muscle movements

promethazine (Phenergan): drowsiness, involuntary muscle movements

trimethobenzamide hydrochloride (Tigan): involuntary muscle movements

Second-Line Agents

metoclopramide (Reglan): diarrhea, involuntary muscle movements

dronabinol (Marinol): drowsiness, confusion, habit-forming

Third-Line Agents (combination use recommended)

ondansetron (Zofran): headache, constipation

granisetron (Kytril): headache, constipation

The Traditional Chinese Medical Approach

Traditional Chinese Medicine (TCM) offers strategies that many people with HIV find simple to use as well as effective. Both acupuncture and herbal regimens are intended to help support gastrointestinal integrity and manage drug side effects, and thereby support adherence to treatment regimens.

Tom Sinclair, MS, L.Ac. (licensed acupuncturist), with the Immune Enhancement Project (IEP) in San Francisco, explained that from a TCM perspective the first step is to establish the underlying cause of nausea. The second step is to determine the most appropriate herbal preparation or formula for treating it. Often, teas are made by brewing fresh roots or herbs at home. Mild ginger, mint and chamomile teas are commonly recommended. "Curing Pill" is the name of an herbal TCM patent product often used for nausea and vomiting. Another herbal product, "Shen Chu" (massafermentata), can be found in Chinese herbalist shops. Other TCM suggestions for ameliorating nausea and vomiting include eating oat bran, rice broth and acidophilus on a regular basis to promote gastrointestinal balance and stability.

Acupuncture and acupressure are also used to treat nausea. Currently, IEP is evaluating a product called a Relief Band in collaboration with the manufacturer, Maven Laboratories. The Relief Band is essentially a type of bracelet designed to control nausea. Worn on the wrist, it provides stimulation of the acupuncture point called paracardiam 6 (P6), located 3 finger-breadths below the wrist. In the 1996 Journal of the Royal Society of Medicine, a metanalysis of 33 acupuncture trials concluded that stimulation of the P6 acupuncture point through conventional acupuncture treatment seems to be an effective technique for controlling nausea in cancer patients.

Other Alternatives

In other reports, behavioral therapy such as progressive muscle relaxation training has helped some people decrease the frequency of nausea and vomiting. Elsewhere, psychological -- especially biofeedback -- therapies, have been helpful for controlling chronic symptoms and relieving pain. Because adequate control of nausea and vomiting increases patients' ability to continue taking treatment and improves quality of life, supplemental psychological support for patients, particularly those suffering from chronic nausea and pain, is recommended.

Medical Marijuana

Medical marijuana bridges the arenas of alternative and standard therapy. Marijuana has been widely reported to benefit persons suffering from nausea and vomiting (as well as pain and loss of appetite), such as people undergoing cancer treatment and people with AIDS. Anecdotal reports of the plant's medicinal value led to the manufacture of synthetic tetrahydrocannabinol (THC), an active ingredient in marijuana. Presently, synthetic THC is manufactured and marketed as the oral drug dronabinol (Marinol). Dronabinol is effective for some people in controlling nausea, improving appetite and enabling food intake. However, a person who is vomiting may be unable to take or benefit from dronabinol. Also, dronabinol may cause considerable drowsiness. Advocates of medical marijuana claim that smoked marijuana has advantages in terms of the form of administration and the individualized dosing and timing possible. Another benefit of smoking is the immediacy of relief, compared to anti-nausea medications including dronabinol, which sometimes require a few hours to bring relief.

Due to legal restrictions, however, the effectiveness of medical marijuana has not been studied in a controlled manner. Under federal law, marijuana is an illegal, controlled substance. Since the passage of voter propositions last November in California and Arizona, the drug's status is unclear in those states. Although the propositions provided for the recommendation by licensed physicians of marijuana for medical use by patients with AIDS and other life-threatening illnesses, the consequences for physicians who recommend medical marijuana and patients who use it are not yet clear.

Simple Nutritional Interventions

It is particularly important for people with HIV disease to maintain nutritional health, which can be difficult when nausea and vomiting are present. For short-term nausea and vomiting, avoiding solid foods and sipping flat, caffeine-free soda in small amounts may bring adequate relief. For chronic symptoms, seek the assistance of a dietician, who can assess dietary patterns and intake, and design an individualized plan for optimal nutritional health.

The following guidelines may help alleviate nausea:

• eat small amounts of food every few hours
• if there is a pattern to nausea, eat more during periods known to involve less nausea
• eat dry foods like toast, crackers or dry cereal at any time, especially shortly after waking eat bland, simple foods such as chicken soup or broth, rice, pasta, bananas, jello, pudding and hot cereal (farina, oatmeal, cream of wheat)
• avoid greasy or fried foods, and use little or no margarine or butter; fats are difficult to digest and may be problematic for persons taking saquinavir
• do not eat and drink at the same time; drink liquids between meals or 30-60 minutes before or after eating
• avoid lying down for at least an hour after eating; if you must rest, sit down or lean back with your head higher than your feet
• keep the room temperature cool
• if drinking liquids does not worsen nausea or vomiting, drink large amounts of fluids such as water, caffeine-free soda (especially clear carbonated sodas like ginger ale or 7-Up), broth or bouillon
• drink electrolyte preparations like Pedialyte or Gatorade, or a mixture of 1 teaspoon of salt, 1 tablespoon of sugar and 1 liter of water
• avoid caffeinated drinks, which cause the kidneys to increase excretion of liquids (note: Coca-Cola syrup is sometimes used to treat nausea)
• sip beverages slowly
• drink liquids that have been allowed to warm or cool to room temperature (extreme temperatures may be difficult to tolerate)
• if cold does not increase nausea, eat popsicles, ice cubes made with juice or tea, or sorbet (alternate ways to take in fluids)

Conclusion

Persistent or severe nausea and vomiting should be assessed and treated. Often, effective control of nausea will prevent vomiting. When nausea and vomiting are likely, e.g., in a person with a history of nausea, prophylactic treatment may be ideal. A wide variety of approaches to managing nausea are available, ranging from standard antiemetic drugs, to simple and practical steps like dietary modifications (probably best for mild, transient nausea), to alternative therapies like acupuncture and TCM.

Because the causes of nausea and vomiting are rarely straightforward, and because the perception of the severity of nausea varies widely from person to person, strategies to manage nausea and vomiting must be individualized. Physicians or pharmacists should be consulted when compliance with drug regimens is impaired or threatened by nausea and vomiting.

Leslie Hanna is Associate Editor of BETA.

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