Thursday, July 24, 2008

Gastroparesis

Gastroparesis At A Glance

  • Gastroparesis is a disease of the muscles of the stomach or the nerves controlling the muscles that causes the muscles to stop working.
  • Gastroparesis results in inadequate grinding of food by the stomach and poor emptying of food from the stomach into the intestines properly.
  • The primary symptoms of gastroparesis are nausea and vomiting.
  • Gastroparesis is best diagnosed by a test called a gastric emptying study.
  • Gastroparesis usually is treated with nutritional support, drugs for treating nausea and vomiting, drugs that stimulate the muscle to contract, and, less often, electrical pacing and surgery.
  1. Gastroparesis means paralysis of the muscles of the stomach. Gastroparesis results in delayed emptying of food from the stomach into the small intestine. The stomach is a hollow organ composed primarily of muscle that serves as a storage container for food. Food in the stomach is ground into tiny pieces by the constant churning that is generated by the contractions of the stomach’s muscles. Once the food has been adequately ground, it slowly is emptied from the stomach into the intestine in a metered fashion. Only food ground into small particles can be emptied from the stomach in a normal fashion, and smaller particles are digested better in the intestine. Moreover, the metering process allows the emptied food to be well-mixed with the digestive juices of the intestine, pancreas, and liver (bile) and to be absorbed well from the intestine.
  2. When the stomach’s muscles are paralyzed, food is not thoroughly ground and does not empty into the intestine normally. Since the muscular mechanisms whereby ground, solid food and liquid food are emptied from the stomach are different, there may be delayed emptying of solid food (most common), solid and liquid food (less common), or liquid food alone (least common).
  3. The primary symptoms of gastroparesis are nausea and vomiting. Other symptoms of gastroparesis include abdominal pain, bloating, early satiety (feeling full quickly when eating), and in severe cases, weight loss due to a reduced intake of food because of the symptoms. Reduced intake of food and restriction of the types of food that are eaten can lead to nutritional deficiencies.
  4. The vomiting of gastroparesis usually occurs after meals; however, with severe gastroparesis, vomiting may occur without eating due simply to the accumulation of secretions in the stomach. The characteristic vomiting happens several hours after a meal when the stomach is maximally distended by the presence of food and secretions stimulated by the meal. Since the grinding action of the stomach is absent, the vomited food often remains in larger pieces and is easily recognized. (Contrast this with the more common type of vomiting in which the food appears as small, uniform, unidentifiable particles.)
  5. Other, less frequent effects of gastroparesis are the promotion of gastroesophageal reflux disease (GERD) and malnutrition.

Causes:
Gastroparesis can be caused either by diseases of the stomach’s muscles or the nerves that control the muscles, though often no specific cause is identified. The most common disease causing gastroparesis is diabetes mellitus which damages the nerves controlling the stomach muscles. Gastroparesis also can also result from damage to the vagus nerve, the nerve that controls the stomach’s muscles, that occurs during surgery on the esophagus and stomach. Scleroderma is an example of a disease in which gastroparesis is due to damage to the stomach’s muscles. Occasionally, gastroparesis is caused by nervous reflexes, for example, when the pancreas is inflamed (pancreatitis). In such cases, neither the nerves nor the muscles are diseased, but messages are sent through nerves from the pancreas to the stomach which prevents the muscles from working normally.

Other causes of gastroparesis include:

  1. imbalances of minerals in the blood such as potassium, calcium or magnesium,
  2. medications (such as narcotic pain-relievers), and
  3. thyroid disease.

According to UCSF, "American Gastroenterological Association Technical Review on the Diagnosis and Treatment of Gastroparesis" : "Viruses that have been implicated in rare cases include Cytomegalovirus, Epstein–Barr virus, and varicella zoster. However, the responsible organism remains elusive in most patients with postviral gastroparesis."

Gastroparesis can occur as an isolated problem or it can be associated with paralysis of other parts of the intestine, including the esophagus, small intestine, and colon.

Diagnosing:

  • Gastric Emptying Study The most common method for diagnosing gastroparesis is a nuclear medicine test called a gastric emptying study which measures the emptying of food from the stomach. For this study, a patient eats a meal in which the solid food, liquid food, or both contain a small amount of radioactive material. A scanner (acting like a Geiger counter) is placed over the stomach for several hours to monitor the amount of radioactivity in the stomach. In patients with gastroparesis, the food takes longer than normal (usually more than several hours) to empty into the intestine.

  • The antro-duodenal motility study is a study that can be considered experimental that is reserved for selected patients. An antro-duodenal motility study measures the pressure that is generated by the contractions of the muscles of the stomach and intestine. This study is conducted by passing a thin tube through the nose, down the esophagus, through the stomach and into the small intestine. With this tube, the strength of the contractions of the muscles of the stomach and small intestine can be measured at rest and following a meal. In most patients with gastroparesis, food (which normally causes the stomach to contract vigorously) causes either infrequent contractions (if the nerves are diseased) or only very weak contractions (if the muscle is diseased).

  • An electrogastrogram, another experimental study that sometimes is done in patients with suspected gastroparesis, is similar to an electrocardiogram (EKG) of the heart. The electrogastrogram is a recording of the electrical signals that travel through the stomach muscles and control the muscles' contractions. An electrogastrogram is performed by taping several electrodes onto a patient's abdomen over the stomach area in the same manner as electrodes are placed on the chest for an EKG. The electrical signals are recorded at rest and after a meal. In normal individuals, there is a regular electrical rhythm just as in the heart, and the power (voltage) of the electrical current increases after the meal. In most patients with gastroparesis, the rhythm is not normal or there is no increase in electrical power after the meal. Although the gastric emptying study is the primary test for diagnosing gastroparesis, there are patients with gastroparesis who have a normal gastric emptying study but an abnormal electrogastrogram. Therefore, the electrogastrogram is useful clinically primarily when the suspicion for gastroparesis is high but the gastric emptying study is normal or borderline abnormal.

  • GI Endoscopy A physical obstruction to the emptying of the stomach, for example, a tumor that compresses the outlet from the stomach or scarring from an ulcer, may cause symptoms that are similar to gastroparesis. Therefore, an upper gastrointestinal (GI) endoscopy test usually is performed to exclude the possibility of an obstruction as the cause of a patient's symptoms. (Upper GI endoscopy involves the swallowing of a tube with a camera on the end and can be used to visually examine the stomach and duodenum and take biopsies.)
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    Upper GI endoscopy also may be useful for diagnosing one of the complications of gastroparesis, a bezoar. Because of the poor emptying of the stomach, hard to digest components of the diet, usually from vegetables, are retained and accumulate in the stomach. A ball of undigested, plant-derived material can accumulate in the stomach and give rise to symptoms of fullness or can further obstruct the emptying of food from the stomach. Removing the bezoar may improve symptoms and emptying.

  • A computerized tomographic (CT) scan of the abdomen and upper gastrointestinal x-ray series may also be necessary to exclude cancer of the pancreas or other conditions that can obstruct the emptying of the stomach.

Treatment of gastroparesis includes diet, medication, and devices or procedures that facilitate emptying of the stomach. The goals of treatment include:

  1. To provide a diet containing foods that are more easily emptied from the stomach.
  2. Controlling underlying conditions that may be aggravating gastroparesis.
  3. Relieve symptoms of nausea, vomiting and abdominal pain.
  4. Stimulate muscle activity in the stomach so that food is properly ground and emptied from the stomach.
  5. Maintaining adequate nutrition.

  1. Diet. Emptying from the stomach is faster when there is less food to empty, so smaller, more frequent portions of food are recommended. Soft foods (or preferably liquid) that do not require grinding also are emptied more easily. Moreover, in gastroparesis the emptying of liquids often is less severely affected than the emptying of solids. Fat causes the release of hormones that slow down the emptying of the stomach. Therefore, foods low in fat empty faster from the stomach. In patients with severe gastroparesis, sometimes only liquid meals are tolerated.
  2. Controlling underlying conditions. High levels of glucose (sugar) in blood tends to slow gastric emptying. Therefore it is important to lower blood glucose levels in patients with diabetes to near normal levels with diets and medications. Individuals with a deficiency of thyroid hormone (hypothyroidism) should be treated with thyroid hormone. If bezoars are present, they should be removed (usually endoscopically).
  3. Relieving nausea, vomiting, and abdominal pain. Drugs used to relieve nausea and vomiting in gastroparesis include promotility drugs (see discussion that follows) such as metoclopramide (Reglan) and domperidone, anti-nausea medications such as prochlorperazine (Compazine) and promethazine (Phenergan), serotonin antagonists such as ondansetron (Zofran), anticholinergic drugs such as a scopolamine patch (commonly used for treating motion sickness), drugs used for treating nausea in cancer chemotherapy patients such as aprepitant (Emend), and medical marijuana Marinol.
    a. Drugs used to relieve abdominal pain in gastroparesis include.1. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin) and naproxen (Aleve);2. low dose tricyclic antidepressants such as amitriptyline (Elavil);3. drugs that block nerves that sense pain such as gabapentin (Neurontin); and4. narcotics such as tramadol (Ultram) and Fentanyl. Narcotic pain relievers as a group tend to cause constipation and slow emptying of the stomach, and, therefore, should be avoided or used with caution among patients with gastroparesis.
  4. Stimulating muscle activity by: Oral Drugs. There are four oral drugs that are used to stimulate contractions of the stomach’s muscles, referred to as pro-motility drugs. These drugs are:
      • a. cisapride (Propulsid), Cisapride is an effective drug for treating
        gastroparesis; however, it was removed from the market because it can cause serious and life threatening irregular heart rhythms. Despite this fact, it can be obtained for use through the pharmaceutical company that manufactures it (Janssen Pharmaceuticals) under a strictly monitored protocol but only for patients with severe gastroparesis unresponsive to all other measures.

      • b. domperidone Domperidone has not
        been released for use in the US;
        however, it can be obtained if approval is
        obtained for its use from the US
        Food and Drug Administration.

      • c. metoclopramide (Reglan); and

      • d. erythromycin The fourth drug, erythromycin (E-Mycin, Ilosone, etc.), is a commonly-used antibiotic. At doses lower than those used to treat infections, erythromycin stimulates contractions of the muscles of the stomach and small intestine and is useful for treating gastroparesis.

It has been demonstrated recently that tegaserod (Zelnorm), an oral drug used for treating constipation in irritable bowel syndrome (IBS), increases emptying from the stomach just as it does from the colon. Further studies will be necessary to determine just how effective tegaserod is and how it compares to the other medications that are available for treating gastroparesis before its use can be recommended.

There are two important guidelines in prescribing oral drugs for gastroparesis. First, the drugs must be given at the right times, and second, the drugs must reach the small intestine so that it can be absorbed into the body. Since the goal of treatment is to stimulate muscular contractions during and immediately after a meal, drugs that stimulate contractions should be given before meals.
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Most drugs must be emptied from the stomach so that they can be absorbed in the small intestine. The majority of patients with gastroparesis have delayed emptying of solid food, and pills and capsules, like solid food, do not empty well from the stomach. As mentioned previously, many patients with gastroparesis have less of a problem emptying liquids as compared with solid food. Therefore, liquid medications usually are more effective than pills or capsules.
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    • Intravenous drugs.
      Occasionally, patients have such poor emptying of both liquid and solid food from the stomach that only drugs given intravenously are effective. In such patients, intravenous metoclopramide or erythromycin can be used. A third option is octreotide (Sandostatin), a hormone-like drug that can be injected beneath the skin. Like erythromycin, octreotide stimulates short bursts of strong contractions of the muscles in the stomach and small intestine. Due to its greater expense and the need for injection, octreotide is used only when other medications fail.
    • Electrical pacing. Electrical pacing of the stomach is a new method for treating severe gastroparesis. Electrical pacing of the stomach is analogous to cardiac pacing for the treatment of an abnormally slow heartbeat and involves the placement of a pacemaker. The pacemaker usually is placed laparoscopically and does not require a large abdominal incision for entering the abdomen. During placement, wire electrodes are attached to the muscle of the stomach. The wires are brought out through the abdominal wall just beneath the skin. The wires are attached to a small, battery-operated pacemaker that is buried in a surgically created pouch just under the skin. The skin is then sutured so that the pacemaker and wires are beneath the skin. The pacemaker generates electrical impulses that are transmitted by the wires to the muscles of the stomach, and the muscles contract in response to the impulses. Electrical pacing is effective in many patients with severe gastroparesis, but the numbers of patients who have been treated is small. Since electrical pacing of the stomach is relatively new, the long-term effectiveness and safety have not been determined clearly.
    • Surgery. Surgery occasionally is used to treat gastroparesis. The goal of surgery is to create a larger opening between the stomach and the intestine in order to aid the process of emptying the stomach's contents. Alternatively, the entire stomach may be removed. These procedures should be considered only when all other measures have failed because of the potential complications from the surgery. Surgery should be done only by surgeons in consultation with gastroenterologists who are knowledgeable and experienced in caring for patients with gastrointestinal motility disorders (disorders of the nerves or muscles of the gastrointestinal tract that affect digestion and transport of food).

5. Maintaining nutrition Patients with mild gastroparesis usually can be successfully managed with pain relievers and pro-motility medications, but patients with severe gastroparesis often require repeated hospitalizations to correct dehydration, malnutrition and to control symptoms.

Treatment options for dehydration and malnutrition include:

Intravenous fluids to correct dehydration and replenish electrolytes if nutrition is adequate but symptoms occasionally interrupt the intake of even liquid food.

Enteral nutrition which provides liquid food directly into the small intestine, bypassing the paralyzed stomach.

  • Intravenous total parenteral nutrition (TPN) to provide calories and nutrient (TPN is a fluid containing glucose, amino acids, lipids, minerals, and vitamins—everything that is needed for adequate nutrition—intravenously. The fluid usually is delivered into a large vein via a catheter in the arm or upper chest.)
  • Doctors generally prefer enteral nutrition over TPN because long-term use of TPN is associated with infections of the catheter and liver damage. Infection can spread through the blood to the rest of the body, a serious condition called sepsis. Catheter-related sepsis often requires treatment with intravenous antibiotics and removal of the infected catheter or replacement with a new catheter. TPN also can damage the liver, most commonly causing abnormal liver tests in the blood. TPN-induced liver damage usually is mild and reversible (the liver test abnormalities return to normal after cessation of TPN), but, rarely, irreversible liver failure can occur. Such liver failure may require liver transplantation. Enteral nutrition is safe and effective. The two common means of delivering enteral nutrition are via nasojejunal tubes or jejunostomy tubes. The jejunum is the part of the small intestine just past the duodenum, the first part of the small intestine just beyond the stomach. Both naso-jejunal tubes and jejunostomy tubes are designed to bypass the stomach and deliver nutrients into the jejunum where they can be absorbed.
    1. A naso-jejunal tube is a long, thin catheter inserted (usually by a radiologist or a gastroenterologist) via the nostril into the stomach. The tip of the naso-jejunal tube is then advanced past the stomach into the small intestine. Often this must be done during upper GI endoscopy. Liquid nutrients then can be delivered via the naso-jejunal tube into the small intestine. Naso-jejunal tubes generally are safe, but there are cosmetic disadvantages and discomfort of having a tube in the nose. The problems that occur with naso-jejunal tubes are primarily accidental or intentional removal by the patient, blockage of the tube by solidified nutritional solutions, and aspiration (backup of stomach contents into the lungs that can lead to pneumonia).
    2. A jejunostomy is a catheter placed directly into the jejunum. It can be done during standard abdominal surgery, using minimally invasive techniques (laparoscopy), or by a specially-trained radiologist. With a jejunostomy, the catheter passes through the skin on the abdominal wall and directly into the jejunum. Before a jejunostomy is placed, a trial of naso-jejunal nutrition often is given to be certain that the small bowel is not involved with the same motility problem as the stomach and that nutritional liquids infused into the small intestine will be tolerated.

      If gastroparesis is caused by a reversible problem, for example pancreatitis, the condition will subside when the underlying problem resolves. In some diabetics, better control of their blood sugar will improve emptying of the stomach. If there is no reversible cause, gastroparesis rarely resolves. In fact, it may become worse with time. Gastroparesis is particularly difficult to treat when there are accompanying motility disorders of the muscles of the small intestine.

      What is new in gastroparesis?

      The newest experimental treatment for gastroparesis is injection of botulinum toxin into the pylorus. The pylorus is the narrow channel through which food passes from the stomach to the duodenum. The pylorus, like the stomach, is a muscular organ. The pylorus is closed most of the time due to continuous contraction of the pyloric muscle. Intermittently it opens and allows secretions from the stomach to enter the small intestine. After meals, the pylorus is very important for metering the emptying of the stomach. In gastroparesis, although the muscles of the stomach are weak all of the time, the muscle of the pylorus remains strong and contracted and the pylorus relatively closed. It was hypothesized that if the strength of the pyloric muscle was reduced, food might empty from the stomach more readily. Although a surgical procedure, termed pyloroplasty, to enlarge the pylorus has been used in the past to treat problems with emptying of the stomach, it is major surgery and has had mixed results with respect to its efficacy. More recently, relaxation of the pyloric muscles has been produced by injecting botulinum toxin (Botox) into the pylorus. Although results have been good, the procedure has not been studied enough to recommend its use unless it is part of a research protocol.

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