What is Heartburn and Gastroesophageal Reflux Disease?
Gastroesophageal Reflux Disease and Heartburn.
The esophagus, commonly called the food pipe, is a narrow muscular tube, about nine
and a half inches long, that begins below the tongue and ends at the stomach. It consists
of three basic layers: an outer layer of fibrous tissue, a middle layer containing
smoother muscle, and an inner mucous membrane which contains numerous tiny glands. The
esophagus is narrowest at the top and bottom; it also narrows to a lesser degree in the
middle, where it passes the aorta. Wave-like muscle contractions, known as peristalsis,
move food down through the esophagus and into the stomach. In the stomach, acid and
various enzymes, notably hydrochloric acid and pepsin, break down and digest the starch,
fat, and protein in the food. The lining of the esophagus itself offers a weak defense
against stomach acid and other harmful substances. Of particular importance in protecting
the esophagus is the lower esophageal sphincter (LES), which is a band of muscle
around the bottom of the esophagus where it meets the stomach. The LES opens after a
person swallows to let food enter the stomach and then immediately closes to prevent
regurgitation of the stomach contents, including gastric acid. It maintains this pressure
barrier until food is swallowed again. If, in spite of LES pressure, there is some acid
back-up (reflux), an additional defense mechanism -- the peristaltic action of the
esophagus -- pushes the residue back down into the stomach.
If the LES or the peristaltic action is impaired or other protective mechanisms fail, then acid and other substances back up into the esophagus from the stomach, causing the condition known as gastroesophageal reflux disease (GERD). Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful. The primary common symptoms of GERD are heartburn (a burning sensation in the chest and throat) and regurgitation (a sensation of acid backed up in the esophagus). In most people, the symptoms are short-lived and occur infrequently. In about 20% of cases, however, the condition becomes chronic. In such cases, the acid can cause irritation, inflammation, and even erosion of the esophagus (a condition called esophagitis). In a small percentage of chronic patients, a serious form of GERD called Barrett’s esophagus may eventually develop, in which the erosion can lead to cancerous changes in the tissue lining of the esophagus. It should be noted that symptoms of GERD may be present without any signs of injury to the esophagus.
What Causes Gastroesophageal Reflux Disease
Mild temporary heartburn caused by overeating acidic foods can happen to anyone,
particularly when bending over, taking a nap, or engaging in lifting after a large meal
high in fatty acidic foods. Persistent gastroesophageal reflux disease (GERD), however,
may be due to one or more pathological factors, which include malfunction of the lower
esophageal sphincter muscles (LES), defects in the mucous membrane, peristalsis problems,
over-acidic stomach contents, and other problems. Some people may be sensitive to
digestive factors other than acid; such substances can cause GERD symptoms but are likely
to be missed as causal agents.
Malfunction of the Lower Esophageal Sphincter (LES) Muscles.
The band of muscle tissue called lower esophageal sphincter (LES), which is
responsible for closing and opening the lower end of the esophagus, is essential for
maintaining a pressure barrier against contents from the stomach. If it loses tone, the
LES will not constrict completely after food is emptied into the stomach; in such cases,
acid from the stomach backs up into the esophagus. The LES is a complex area of smooth
muscles and its function can be impaired by various hormones, dietary substances, drugs,
and nervous system factors.
Impaired Stomach Function.
In one study, over half of GERD patients showed abnormal nerve or muscle function in
the stomach, which caused impaired motility, an inability of the muscles to contract
normally. This causes delays in stomach emptying, increasing the risk for acid back-up.
Hiatal Hernia.
Until recent years, it was commonly believed that most cases of persistent heartburn
were caused by hiatal, or hiatus hernia - a protrusion of the stomach from the abdomen up
into the chest. Although hiatal hernia may impair LES function, studies have failed to
find a close causal association between gastroesophageal reflux and hiatal hernia. Some
studies indicate that people with both GERD and hiatal hernia do have more severe
gastroesophageal reflux.
Medical Conditions that Contribute to GERD.
About half of asthmatic patients also have GERD. Some experts speculate that the
coughing and sneezing accompanying asthmatic attacks cause changes in pressure in the
chest that can trigger reflux. Certain asthmatic drugs including theophylline and other
medications that dilate the airways may relax the LES and contribute to GERD. It is not
entirely clear, however, whether asthma is a cause or effect of GERD [see also, How
Serious is Gastroesophageal Reflux Disease?, below] . Other conditions, such as
Crohn’s disease, can cause inflammation in the esophagus. Other disorders that may
affect areas that can contribute to GERD include diabetes, peptic ulcers, lymphomas, and
cancer.
Hypersensitive Esophagus.
When the esophagus appears normal but GERD symptoms are present, the cause may be an
exaggerated, or hyperactive, response to irritants that causes the immune system to
produce factors that produce inflammation in the esophagus.
Other Causes of GERD.
Weakened peristaltic movement in the esophagus may contribute to GERD. If the mucous
membrane is impaired, even a normal amount of acid can harm the esophagus. Pressure on the
abdomen caused by factors such as obesity or tight clothing can contribute to acid back-up
into the esophagus. A recent study suggested that food allergies may be responsible for
gastroesophageal reflux disease in children.
Who Gets Gastroesophageal Reflux Disease?
Gastroesophageal reflux disease is very common. Studies have shown that 36% to 44% of adults experience heartburn at least one a month, 14% every week and 7% once a day. One study reported that 20% of people had frequent symptoms of GERD but that very few of them sought help for the condition. People of all ages are susceptible to GERD. Elderly people with GERD tend to have a more serious condition than younger people with the problem.
Foods and Eating-Pattern Risk Factors.
Anyone who eats a heavy meal, particularly if one subsequently lies on the back or
bends over from the waist, is at risk for an attack of heartburn. Anyone who snacks at
bedtime is at high risk for GERD. Foods that can weaken LES tone include garlic, onions,
chocolate, fat, alcohol, peppermint, spearmint, and coffee. Caffeinated drinks and
decaffeinated coffee increase acid contents in the stomach. Other carbonated beverages
increase the risk for symptoms of GERD by bloating the stomach and causing pressure that
forces acid to back up into the esophagus.
Smoking and Alcohol.
Alcohol can irritate the mucous membrane of the esophagus and relax the LES. In
concentrations of 40% (80 proof), alcohol has been shown to cause erosion and bleeding of
the stomach lining in both animals and humans. On the other hand, some studies have shown
that small amounts of alcohol may actually protect the mucosal layer. Smoking can also
reduce muscle function, increase acid secretion, reduce prostaglandins and bicarbonate
production, and decrease mucosal blood flow.
Drugs that Increase the Risk for GERD.
A number of drugs and foods can cause the LES to relax and function poorly. Drugs that
have this effect include calcium channel blockers, anti-cholinergics, beta- and
alpha-adrenergic agonists, dopamine, sedative, and common pain relievers. Calcium channel
blockers and anti-cholinergics also weaken the peristaltic action of the esophagus and
slow stomach emptying. The anti-osteoporosis drug alendronate (Fosamax) can cause damage
to the esophagus. Patients should take this drug with six to eight ounce of water (not
juice or carbonated or mineral water) on an empty stomach in the morning and should remain
upright for 30 minutes afterward.
Antibiotics can also affect the mucus membrane, making it more vulnerable to acids. Potassium and iron pills are also corrosive and can cause ulcers (erosions) in the esophagus.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are common culprits in causing ulcers in the stomach. Until recently there was no strong evidence that their use harmed the esophagus. A 1997 study reported however, that elderly people who took NSAIDs and also had GERD appeared to be at higher risk for complications, particularly strictures--abnormal narrowings of the esophagus--and also chest pain and Barrett’s esophagus. There are dozens of NSAIDs including aspirin, ibuprofen (Motrin, Advil, Nuprin, Rufen) naproxen (Aleve), piroxicam (Feldene), diflunisal (Dolobid), indomethacin (Indocin), flurbirpofen (Ansaid), ketorolac (Toradol), ketoprofen (Actron, OrudisKT), and diclofenac (Voltaren). Most likely, taking an occasional aspirin or other NSAID will not harm someone who has GERD and no other risk factors for or indications of ulcers. Tylenol (acetaminophen) is a good alternative for those who want to avoid NSAIDs.
Children at Risk.
About 65% of all babies regurgitate some amount of milk occasionally. Some simply spit
up milk; others vomit large amounts after feedings. The severity of the vomiting, however,
is not related to the severity of GERD. A condition that warrants further investigation is
indicated only by complications, including failure to thrive or pneumonia [see How
Serious is Gastroesophageal Reflux Disease?, below]. Children at highest risk are
those with neurologic impairment and chronic lung disease.
Pregnant Women.
Pregnant women are particularly vulnerable to GERD in their third trimester as the
growing uterus puts increasing pressure on the stomach. Heartburn in such cases is often
resistant to dietary interventions and even antacids.
People with Asthma.
People with asthma are at very high risk for GERD; at this point it is unclear whether
asthma cause GERD or vice versa.
Genetic Factors.
Genetic factors may play a role in susceptibility to Barrett’s esophagus, a
precancerous condition caused by very severe gastroesophageal reflux. One expert believes
that an inherited risk exists in most cases of GERD.
What Are the Symptoms of Gastroesophageal Reflux Disease?
Typical Symptoms.
The primary symptoms of gastroesophageal reflux are heartburn, a burning sensation
that radiates up from the stomach to the chest and throat, and regurgitation, in which the
patient can feel the acid backing up. Sometimes it regurgitates as far as the mouth and
may come out forcefully as vomit or experienced as a "wet burp". Up to half of
GERD patients have dyspepsia, which is a combination of heartburn, fullness in the
stomach, and nausea after eating. The symptoms are most likely to occur after a heavy meal
while bending over, lifting, or lying down -- particularly on one’s back. It should
be noted that the severity of symptoms does not necessarily reflect actual injury in the
esophagus. For example, Barrett’s esophagus, which causes precancerous changes in the
esophagus, may cause few symptoms, particularly in elderly people. On the other hand,
people can suffer severe heartburn without actual damage to the esophagus.
Atypical Symptoms.
Between 10% and 15% people with GERD have so-called atypical symptoms, which occur
with or without heartburn or acid regurgitation. These symptoms may resemble other serious
conditions and may require an intensive diagnostic work-up.
Chest Pain. GERD is a common cause of chest pain. It is very important to differentiate chest pain caused by GERD from that caused by heart conditions, particularly angina and heart attack. In general, if the pain does not occur after exertion or is worse at night, then it is less likely to be due to a heart problem. (Chest pain from either GERD or from severe angina, however, can occur after a heavy meal.) It should be noted that the two conditions often coexist; some patients with coronary artery disease may develop anginal chest pain from acid reflux. Some experts believe that this is because the acid in the esophagus of such patients may activate nerves that temporarily impair blood flow to the heart.
Bleeding. Dark-colored, tarry stools (indicating the presence of blood) or vomiting blood may occur if ulcers have developed in the esophagus. This is a sign of severe damage and requires immediate attention.
Trouble Swallowing and Choking. Almost half of GERD patients report having trouble swallowing (dysphagia), usually caused by a narrowed esophagus. If the esophagus has narrowed severely, patients may even choke or experience the sensation that food is trapped behind the breast bone. These are symptoms of serious esophageal damage or of temporary spasm that narrow the tube. Choking may also occur because of spasm in the larynx.
Coughing and Asthmatic Symptoms. Asthmatic symptoms, including coughing and wheezing, may occur. GERD is, in fact, the second most common cause of persistent coughing, which can occur without other symptoms of asthma.
Chronic Nausea and Vomiting. Nausea that persists for weeks or even months that is not attributable to a common cause of stomach upset may be a symptom of acid reflux. Vomiting may also occur, and, in rare cases, patients vomit as often as once a day. Other causes of chronic nausea and vomiting that should be ruled out include ulcers, stomach cancer, obstruction, or pancreas or gallbladder disorders.
Other Problems in the Throat. If stomach acid reaches the larynx (the voice box), it causes a condition called acid laryngitis. This can cause hoarseness, a dry cough, the feeling of having a lump in the throat, and the need to clear the throat repeatedly. GERD is a common cause of chronic sore throat and may also trigger persistent hiccups.
How Serious is Gastroesophageal Reflux Disease?
General Outlook.Barrett’s Esophagus.
Barrett’s esophagus is the most serious form of GERD. It is caused by chronic and
severe exposure to acid. In such cases, cellular changes can occur that, over time, may
develop into cancer. Barrett’s esophagus is, in fact, the only proven risk factor for
cancer in the mucus lining of the esophagus, which is one of the most rapidly increasing
cancers in North America. Fortunately, it occurs only in a small number of GERD patients;
at risk are patients who develop GERD at an early age and whose symptoms last longer than
most. To date, none of the standard GERD treatments appear to reverse the cellular damage
done after Barrett’s esophagus has developed. Patients with this condition need to be
monitored periodically with endoscopy and biopsy in order to detect cancer early [see
How Is Gastroesophageal Reflux Diagnosed? below].
Bleeding.
If ulcers (erosions) develop in the esophagus, they can cause bleeding. Persistent
bleeding can result in iron deficiency anemia, and, in some cases, may even require
emergency transfusions. This condition may occur even without heartburn or other warning
symptoms.
Respiratory Disorders.
Asthma. GERD is a suspect in causing asthma attacks in patients with this
respiratory disorder who have no allergies or history of lung disease. In such cases, some
experts believe that the acid leaking from the lower esophagus stimulates the vagus nerves
that are located nearby. These stimulated nerves, in turn, trigger the airways in the lung
to constrict, causing asthmatic symptoms. In some cases, asthma may be triggered by
aspirated fluid from the esophagus. On the other hand, some researchers think that asthma
is actually a cause of GERD [see What Causes Gastroesophageal Reflux Disease? above].
People with both asthma and GERD report higher than normal rates of choking during the
night, burning at the back of the throat, sore throat, regurgitation, and hoarseness.
Other Respiratory Conditions. In addition to asthma, people with GERD appear to have an above-average risk for a number of respiratory disorders. These include chronic bronchitis, emphysema, pulmonary fibrosis, and pneumonia. If a person inhales fluid from the esophagus (aspirates) into the lungs, serious pneumonia can occur. It is not yet known whether treatment of GERD would also reduce the risk fro these respiratory conditions.
Sleep Apnea.
Acid reflux can cause spasms of the vocal cords (larynx), thereby blocking the flow of
air to the lungs. One study reported that such spasms may cause sleep apnea in adults. In
sleep apnea, breathing stops repeatedly but temporarily during sleep. Patients often
experience restless sleep, morning headaches, and afternoon drowsiness. In time, they may
develop hypertension, which increases their risk of heart attack and stroke.
Dental Problems.
Dental erosion is very common problem in GERD patients due to the acid backing up into
the mouth and eroding enamel in the teeth.
Severe Dysphagia.
If the esophagus becomes severely injured, over time narrowed regions called
strictures can develop, which may impair swallowing (dysphagia). Stretching procedures or
surgery may be required to restore normal swallowing. Paradoxically, strictures may
actually improve other GERD symptoms by helping to prevent acid from traveling up the
esophagus.
GERD in Infants and Children.
Gastroesophageal reflux disease in children, as in adults, is usually mild, causing
only frequent spitting up. In severe cases, however, GERD increases susceptibility for
severe vomiting, impaired growth, a syndrome of choking, coughing and gagging, and
pneumonia. Acid reflux that causes spasms in the larynx that block the airways in infants
can be life-threatening. Some experts believe this action may contribute to sudden infant
death syndrome (SIDS). More research is needed to determine whether this association is
valid.
How Is Gastroesophageal Reflux Diagnosed?
In the great majority of cases, a diagnosis of gastroesophageal reflux disease is straightforward, particularly if heartburn and acid regurgitation are present and are lessened by taking antacids for short periods. Laboratory or invasive tests are required only if heartburn is persistent or if atypical symptoms or complications, such as signs of bleeding or difficulty in swallowing, are present.
Barium-Swallow Radiograph.
A barium swallow radiograph (x-ray) is used for identifying structural abnormalities
and severe esophagitis (inflammation). When taking this test, the patient drinks a
solution containing barium, then x-rays are taken, which can show stricture, active ulcer
craters, hiatal hernia, erosion, or other abnormalities. This test cannot, however, reveal
mild irritation and may represent the normal reflux of the barium solution for GERD.
Upper Endoscopy.
Upper endoscopy, also called esophagogastroduodenoscopy, is more accurate than a
barium-swallow radiograph, although it is more invasive and expensive. Endoscopy may be
performed either in a hospital or in a doctor’s office. The doctor first administers
a local anesthetic using an oral spray and an intravenous sedative to suppress the gag
reflex and to relax the patient. Next, the physician places an endoscope -- a thin,
flexible plastic tube -- into the patient’s mouth and down the esophagus. A tiny
camera in the endoscope allows the physician to see the surface of the esophagus and to
search for abnormalities, including damage to the mucus lining and hiatal hernia. If a
patient has moderate to severe symptoms and the procedure reveals injury in the esophagus,
usually no further tests are needed to confirm a diagnosis of GERD. The test is not
fool-proof, however; a visual view misses about half of esophageal abnormalities. After
conducting a biopsy (the removal of small tissue sections), however, microscopic
examination may detect tissue injury indicative of GERD. Tissue samples can also be used
to rule out or confirm cancer or infective organisms, such as yeast (Candida albicans) or
viruses, such as herpes simplex and cytomegaloviruses. Such organisms are more likely to
occur in people with impaired immune systems. Period endoscopy is important for detecting
early cancer in people with Barrett’s esophagus. For such patients, it is recommended
that endoscopy be performed every other year in those with normal cells and then annually
if precancerous changes are detected.
PH Monitor Examination.
The pH monitor examination uses a tubular probe that is inserted through the nose into
the esophagus. The probe is left in place for 24 hours while the patient engages in normal
activities. The probe measures the amount of acid backing up in the esophagus and the
pattern of its occurrence during the day. This information is useful when GERD symptoms
are present but endoscopy has not detected damage to the mucous lining in the esophagus.
It is particularly beneficial for determining if respiratory symptoms, including wheezing
and coughing, are related to reflux episodes in patients with unexplained asthma. Because
it is only a measure of acidic content, however, other digestive agents in the stomach
content that can be causing harm may be overlooked.
Manometry.
Manometry is a test that measures internal pressure. Such measurements of the pressure
exerted by the lower esophagus sphincter muscles may help determine which patients need or
are appropriate candidates for surgery. It is also useful for detecting muscle action
abnormalities, including impaired stomach motility (an inability for the muscles to
contract normally). The standard procedure for GERD is not effective in people with
abnormal stomach motility. Manometry may also be used to detect impaired peristalsis or
other motor abnormalities in people with chest pain and GERD. To reproduce chest pain
during manometry, the patient may be given acid and a drug to stimulate nerves that affect
the heart.
Other Tests.
Stool tests may show traces of blood that are not visible, and blood tests may reveal
anemia in those who have bleeding ulcers. For patients with chest pains in which the
diagnosis is uncertain, a procedure called the Bernstein test may be useful, although it
is rarely used now. It employs concentrated hydrochloric acid and a neutral solution,
which are infused separately into the esophagus. If the acid infusion causes chest pain
and the neutral solution doesn’t, then a diagnosis of GERD is established.
What Are the Treatments for Heartburn and Gastroesophageal Reflux Disease?
General Guidelines for Preventing and Treating GERD.
Most cases of gastroesophageal reflux can be managed with lifestyle changes and the
use of antacids for episodes of heartburn. In about 20% of patients, however, more
intensive treatment may be needed to prevent persistent acid reflux. In such cases, the
aim of drug therapy is to reduce the amount of acid present and improve any abnormalities
in muscle function of the lower esophagus sphincter (LES), the esophagus, or the stomach.
Drug failure can occur in some people, which may be due to less effective action by the
drug on acid reflux during the night, back-up in the esophagus of harmful substances other
than stomach acid, reflux of bile (a fluid composed mostly of water, bile salts, lecithin,
and cholesterol that is present in the small intestine and gallbladder), or other factors.
Even when symptoms are completely relieved by medication, they usually return within a few
months after drug treatment has stopped. Surgery may be indicated if drug treatments have
failed, in those with complications, or in younger people with chronic GERD who face a
lifetime of expense and inconvenience with maintenance drug treatment. The increasing
experience with the use of minimally invasive surgical procedure is causing some experts
to recommend surgery as a possible first treatment option for patients with chronic GERD
who now rely on long-term drug treatment. They argue that acid-suppressing treatment does
not heal the condition, while surgery offers a possible cure. This is important because
persistent GERD appears to be much more serious than previously believed, and the
long-term safety of acid-suppression is still uncertain.
Lifestyle Changes.
Dietary Changes. People with heartburn should first try lifestyle and dietary
changes. In one study, 44% of patients who experience symptoms of GERD reported
improvement after changing their diet. People with heartburn should avoid or reduce
consumption of foods and beverages that contain caffeine, peppermint, spearmint, alcohol,
and fat. Both caffeinated and decaffeinated coffee increases acid secretion. All
carbonated drinks increase the risk for GERD.
Prevention of Nighttime GERD. Lying flat can produce intense acid reflux. After meals, chronic heartburn sufferers should take a walk or, at the very least, remain upright. Bedtime snacks should be avoided. To help keep acid in the stomach at night, a patient may need to raise the bed at an angle using four- to six-inch blocks at the head of the bed or a wedge-support that elevates the top half of the body so that the patient’s body is tilted up. Extra pillows that only raise the head actually increase the risk for reflux.
Chewing Gum. Because saliva helps neutralize acid and contains a number of other factors that protect the esophagus, chewing gum 30 minutes after a meal has been found to help relieve heartburn and even protect against damage caused by GERD. In fact, chewing on anything at all can help, since it stimulates production of saliva.
Avoiding NSAIDs. Many physicians advise GERD patients to avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Aleve), among others. Tylenol (acetaminophen) is a good alternative.
Other Lifestyle Changes. Quitting smoking is, of course, essential. People who are overweight should try to reduce. Clothing that is tight, particularly around the abdomen, should not be worn.
Managing Infants and Children with GERD. Studies have found that infants with gastroesophageal reflux who spend prolonged periods of time in infant seats, including car seats, have more problems with the condition than those who spend waking time on their stomachs. Parents of infants with GERD should discuss their baby’s sleeping position with their pediatrician. Experts strongly recommend that all healthy infants sleep on their backs to help prevent sudden death syndrome. For babies with GERD, however, lying on the back may obstruct the airway. If the physician recommends that such babies sleep on their stomachs, parents should be sure that their infant’s mattress is very firm and possibly tilted up at the head, that there are no pillows, and that the baby’s head is turned so that the mouth and nose are completely unobstructed. During feeding, the child should be positioned vertically and burped frequently. If the baby is fed formula, a mother should ask the doctor about making it thicker to help prevent splashing up from the stomach. Because food allergies may trigger GERD in children, parents may want to discuss with their physicians a dietary plan that starts with a formula using non-allergenic proteins and then adds other foods back one at a time until symptoms are triggered.
Drugs Used for Treating GERD.
General Conditions. A number of drugs are effective in managing both episodic
heartburn and persistent GERD. Over-the-counter antacids, which neutralize digestive
acids, are the first line of drugs for mild symptoms. Also available over the counter are
the H2 blockers, such as Tagamet HB, Pepcid AC, Axid AR, and Zantac 75, which
block acid production. These drugs provide relief for about half of people with chronic
symptoms. Another important class of anti-acid drugs are proton-pump inhibitors
(omeprazole or lansoprazole), which suppress acid production and can relieve symptoms in
almost all people with GERD. Currently they are used only when symptoms are severe and
there is damage to the esophagus lining. Cisapride is the standard drug in a class known
as prokinetics. It does not affect acid production but works on motor function, improving
the muscles action of the esophagus, the LES, and stomach to enhance peristaltic action,
LES pressure, and stomach emptying.
Experts argue about the best way to initiate treatment for GERD with typical symptoms (heartburn and regurgitation) that do not respond to lifestyle change and antacids. Using a so-called step-up approach, the physician first prescribes an H2 blocker drug. If the condition fails to improve, then therapy is "stepped up" to the more powerful proton-pump inhibitor. Other physicians, however, advocate a step-down approach, in which a proton-pump inhibitor, usually omeprazole, is used first. Treatment is then "stepped down" as the patient improves. Some experts believe, however, that by using the more powerful drug first, symptoms of peptic ulcer, if present, may be masked and the condition may persist undiagnosed. They argue that at this time the step-down approach should be reserved or patients who do not respond to conservative therapy or have complications.
A number of studies have investigated combinations of anti-GERD drugs. One study suggested that a combination of over-the-counter antacids and H2 blockers may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD but have different timing. Antacids neutralize the acid in the stomach and work within a few minutes, but their effects do not last more than an hour or so. H2 blockers suppress acid production. It takes between a half-hour to 90 minutes for them to work, but their benefits persist for hours. Because these drugs have different actions, they may be taken in combination without concern that the effects are additive, although some experts believe that antacids may slow down absorption of H2 blockers and reduce their effectiveness. For severe cases, some experts recommend a combination of one of the acid-reducing drugs (either an H2 blocker or a proton-pump inhibitor) with a prokinetic drug (usually cisapride), which works on muscle action. Some suggest that a combination therapy be considered in the following circumstances: when single drugs fail; when the primary symptom is acid regurgitation; when symptoms occur mostly at night; when respiratory problems accompany GERD; when reflux symptoms persist but tests do not show abnormally high acid levels in the esophagus; or when patients are seriously ill and also have severe GERD. It should be noted that combination therapies are expensive and should not be used until other options have failed. For severe cases, some experts believe combination therapy has no benefit over high doses of a proton-pump inhibitor, because symptom severity is most likely due to injury to the esophagus from acid, against which the prokinetic drug has no effect.
It should be noted that none of these drugs cure GERD and that, to date, they do not appear to reverse Barrett’s esophagus. Even when they relieve symptoms completely, the condition usually recurs within months after drugs are discontinued. In chronic cases, they may need to be taken life-long. Drugs that block or neutralize acid also have no effect on regurgitation and so may not be very effective against asthmatic symptoms caused by aspiration. Also of concern are studies that have reported cancerous change in the stomachs of patients taking long-term acid-suppressing drugs -- either H2 blockers or proton-pump inhibitors -- although the risk appears to occur in those who are also infected with the H. pylori bacteria but has not received antibiotic therapy.
Antacids. Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. Despite the many brands, they all rely on various combinations of three basic ingredients, and they all work by neutralizing the acid in the stomach. It has been suggested that they may also stimulate the defensive processes of the stomach, causing increases in bicarbonate and mucous secretion.
There are three basic salts used in various antacids: magnesium, calcium, and aluminum. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. This can lead to kidney failure and is very dangerous. None of the other antacids have this side effect. The most common side effect of antacids containing aluminum salts (Amphogel, Alternagel) is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis. Long-term use of antacids also increases the risk for kidney stones. The aluminum and magnesium salt are usually offered in combination products (Mylanta and Maalox) because this balances the side effects of diarrhea and constipation.
It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten) and H2 blockers ranitidine (Zantac) and famotidine (Pepcid AC). Interactions can be avoided by taking the drugs one hour before or three hours after taking the antacid.
Foaming Agents. Foaming agents are available over the counter and work by forming a barrier that floats over the contents of the stomach, thereby preventing reflux. Such medications may be useful for patients who have GERD but no signs of injury to the esophagus.
H2 Blockers. H2 blockers, also called H2 antagonists, obstruct the actions of histamine, a chemical found in the body that promotes acid secretion in the stomach. Acid secretion is inhibited by these drugs for six to 24 hours and they are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. One major study reported that the H2 blockers are effective in more than 70% of people with mild or intermittent GERD in whom there is no injury to esophagus. In those with moderate symptoms, H2 blockers provide symptom relief in about half of patients. The drugs are usually taken at bedtime; some people may need to take them twice a day. It should be strongly noted that even though these drugs are available without a prescription, patients who use them for self-medication should seek medical advice for persistent heartburn, which may be a symptom of some other condition.
Four H2 blockers are currently available over-the-counter. In spite of different marketing claims, they are all equally effective. They have few side effects and are quite safe. Until it was discovered that H. pylori bacteria was the primary cause of peptic ulcers, H2 blockers were the mainstay for treating the symptoms of this disorder. GERD symptoms are more difficult to resolve than those of peptic ulcers, so higher doses may be needed. The drugs have few side effects. Those most often reported include mild temporary diarrhea, dizziness, rash, nausea, and headache. Long-term acid-suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infections.
Famotidine (Pepcid AC) is the most potent of the H2 blockers. The most common side effect of famotidine is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free of interactions with other drugs.
Cimetidine (Tagamet HB), the first H2 blocker, has been one of the best-selling drugs in the world. Because cimetidine interacts with a number of commonly used medications, including phenytoin (Dilantin), theophylline (Theo-Dur), and warfarin (Coumadin), patients should always inform their physicians of their entire drug regimen. Long-term use of excessive doses (more than 3 grams a day) may also cause impotence or breast enlargement; these problems resolve after the drug is discontinued.
Ranitidine (Zantac 75) was the second H2 blocker to be introduced. Ranitidine’s advantage over cimetidine is that it interacts with very few drugs. Even so, the physician must always be aware of any other drugs a patient is taking. One study found that two daily 75 mg doses of ranitidine was effective for pregnant women with GERD. Animal studies have not shown any adverse effects of ranitidine on pregnancy, although no studies have been conducted on its safety in pregnant women. A common side effect associated with ranitidine is headache, which occurs in about 3% of people who take it.
Nizatidine (Axid AR) is the latest H2 blocker and is nearly free of side effects and drug interactions.
Proton-Pump Inhibitors. Proton-pump or acid-pump inhibitors work by inhibiting the so-called gastric acid pump that is required for the stomach’s cells to secrete acid. Omeprazole (Prilosec) and lansoprazole (Prevacid) are the proton-pump inhibitors currently available by prescription; they are expected to eventually become available over the counter. Pantropazole is under investigation. Proton-pump inhibitors are more effective than either H2 blockers or the prokinetic drug cisapride [see below]. They are currently recommended for patients with moderate symptoms that do not respond to H2 blockers, for those with severe symptoms, those who have respiratory complication, patients who have ulcerated or eroded esophagi, and those who have persistent nausea. Some experts believe, however, that they are the first drug of choice even for patients with milder symptoms, and some studies indicate they are effective even if the esophagus does not show signs of inflammation. Studies report symptom relief in up to 93% of patients who take omeprazole or lansoprazole. In addition to relieving most common symptoms, including heartburn, they are also effective in relieving chest pain and laryngitis caused by GERD. In one study, however, a proton-pump inhibitor taken with cisapride had no effect on regurgitation and was ineffective in controlling asthmatic symptoms in most patients. Side effects are uncommon but may include an allergic reaction, headache, stomach pain, and diarrhea. They should not be used unless necessary by pregnant women or nursing mothers. They appear to be safe and effective for children with severe GERD and may help some avoid surgery. There is some concern that long-term use of proton-pump inhibitors and acid-blocking drugs can increase the risk of stomach cancer by preventing the secretion of acid, thereby causing a condition called atrophic gastritis. Tumors have developed in rats that took omeprazole lifelong and three people who took the drug for a year developed nonmalignant polyps. As with H2 blockers, long-term use of the proton-pump inhibitor in some patients, particularly those who are infected with H. pylori, causes changes in the cells of the stomach that could be precursors to cancer.
Prokinetic Drugs. Prokinetic drugs, the most important of which is cisapride (Propulsid) increases LES pressure, enhances stomach emptying, and improves peristaltic action (the wave-like muscular movement) in the esophagus. It is useful as a primary drug when the esophagus is not injured or eroded by acid reflux and may be beneficial in combination with acid-suppressing drugs, particularly in patients with symptoms such as dyspepsia and nausea, which are indications of muscle abnormalities. The drug is effective as an H2 blocker for acute single episodes and can also be used for maintenance therapy in mild to moderate GERD. It also appears to be safe even in small children. Of concern, however, are reports of heart rhythm disturbances that, in some cases, including in some children, were fatal. These serious effects usually occurred if patients were also taking certain antifungal medications or antibiotics. Patients should discuss these or any other drug interactions with their doctor. Another drug that helps muscle tone in the digestive tract is metaclopramide (Reglan).
Sucralfate. Sucralfate (Carafate) seems to work by adhering to an ulcer crater and protecting it from further damage by the stomach acid and pepsin. It may be used for maintenance therapy in people with mild to moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, including warfarin, phenytoin and tetracycline.
Surgical Treatments for GERD.
Fundoplication. The standard surgical treatment for GERD is fundoplication,
usually a specific variation called Nissen fundoplication. Another form of the procedure,
called Thal fundoplication, may have fewer complications for children. Surgery can cure
many cases of GERD, although it is not very effective for Barrett’s esophagus. It is
recommended for patients whose condition includes one or more of the following:
esophagitis (inflamed esophagus); recurrent or persistent symptoms in spite of drug
treatment; strictures; or evidence of acid reflux as well as asthmatic symptoms caused by
GERD-produced aspiration. Surgery has, until recently, been the primary treatment for
children with severe complications from GERD because drugs either had severe side effects,
were ineffective, or had not been optimized for children. With the introduction of
omeprazole, some children may be able to avoid surgery.
During fundoplication, the far end of the esophagus is wrapped with the fundus (the upper part) of the stomach. The procedure is effective in building LES pressure so that acid reflux is prevented and it appears to enhance stomach emptying. It improves peristalsis in about half of patients, although it may actually cause abnormal peristalsis in about 14% of patients, which, however, does not appear to have much effect on symptoms. About 90% of patients are free of heartburn after the operation. It cures GERD-induced asthmatic or respiratory symptoms in 75% of patients.
Until recent years, standard surgical techniques were used. Increasingly, though, fundoplication is performed using laparoscopy, in which tiny incisions are made in the abdomen and small instruments and a tiny camera are inserted through tubes. There are few complications, although if the fundus is wrapped too tightly, patients may have difficulty swallowing or be unable to burp. Standard fundoplication has few complications, although the complication rate can be very high in children with neurologic abnormalities -- children, who are, unfortunately, at very high risk for GERD in the first place. Laparoscopic fundoplication appears to be safe and effective in people of all ages -- even very small babies. In about 8% patients, it may be necessary to convert conventional surgery during the procedure. The procedure may need to be repeated in some patients because of different factors, including hernia, dysphagia, or recurrent ulcers, but even then results are excellent. The procedure is showing success rates of up to 97% after one year, and in one three-year study 86% of surgical patients were still completely free of heartburn and 10% had only occasional heartburn. Just 4% reported only slight improvement. In those with Barrett’s esophagus, the condition healed or improved in about a third of the cases after surgery. The procedure has little benefit for patients with impaired stomach motility (an inability for the muscles to move spontaneously).
A number of experts now believe that laparoscopy should be considered as primary therapy in patients who would ordinarily be candidates for taking proton-pump inhibitor long-term. They argue that drug treatment cannot cure the problem. Only surgery improves regurgitation and it is far more effective in improving asthmatic symptoms than drug treatment. One study reported that the lifetime costs of surgical treatment are less than treatment using proton-pump inhibitors, assuming a patient took the medication one third of a normal life-span.
Esophagectomy. Esophagectomy is the surgical removal of all or part of the esophagus. Patients with Barrett’s esophagus who are otherwise healthy are candidates for this procedure if endoscopy shows developing cancer.
Ablation Procedure. Procedures using laser or heat probes are being investigated for ablating (removing) injured tissue in the mucus lining of the esophagus. Researchers are hoping that such techniques will be successful in treating precancerous cells and small cancers that are detected in Barrett’s esophagus. Studies on the use of ablation procedures along with aggressive standard anti-GERD drug or surgical treatments are encouraging.
Treatments for Complications of GERD.
Treatments for Bleeding. Endoscopic treatment of bleeding involves using a
probe passed through the endoscopic tube that applies electricity or heat to coagulate
blood and stop the bleeding.
Treatment of Strictures. Strictures (abnormally narrowed regions) may need to be dilated (opened) with endoscopy. Dilation may be performed by inflating a balloon in the passageway. About 30% of patients who need this procedure require a series of dilation treatments over a long duration in order to fully open the passageway. Long-term use of proton-pump inhibitors may reduce this duration.
Phototherapy for Barrett’s Esophagus. An experimental procedure called photodynamic therapy is showing promise for removing local cancers and precancerous tissue found in patients with Barrett’s esophagus.
Where Else Can Information about Peptic Ulcers Be Obtained?
National Digestive Diseases Information Clearinghouse
Call (301-654-3810)
American Gastroenterological Association
Call (301-654-2055)
or on the Internet (http://www.gastro.org)
American Society for Gastrointestinal Endoscopy
13 Elm Street
Manchester, MA 01944
On the Internet (http://www.asge.org/)
Pediatric/Adolescent Gastroesophageal Reflux Association
(PAGER)
Call (301-601-9541)
Children’s Motility Disorder Foundation
Call (800-809-949) or (404-529-9200)
For further information (brochures & video), call 1-800-HRT-BURN.
Modified April 24, 1999 - Four M Engineering, Inc
(Well-Connected, Report #85 March 31, 1998)