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Published in the
Bulletin of Experimental Treatments for AIDS June 1997 issue, by
the San Francisco AIDS Foundation.
June 1997
Table of Contents
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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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Page last updated 2 July 1997
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