Article - Gastroparesis
Arnon Lambroza, M.D.
Clinical Associate Professor of Medicine
Weill Medical College of Cornell University
Gastroparesis is a gastric motility disorder that is characterized by the delayed emptying of gastric contents in the absence of a mechanical obstruction. The characteristic symptoms of gastroparesis include nausea, vomiting, bloating and early satiety. Abdominal pain may be a prominent symptom in some patients. The differential diagnosis of nausea and vomiting is extensive and includes mechanical obstruction, medication side effects, peptic ulcer disease, pancreatic disease, metabolic/hormonal disorders, post-operative states, stress and primary CNS disease. The diagnosis of gastroparesis requires ruling out other causes of nausea and vomiting and documenting an objective delay in gastric emptying.
Gastric emptying is dependent upon complex myoelectrical and mechanical (contractile) events which are coordinated by intrinsic and extrinsic nerves and influenced by hormonal, duodenal and small bowel factors. Readily available tests for assessing gastric function include radionuclide gastric emptying studies, barium studies and breath tests. Less readily available tests include antroduodenal manometry and the electrogastrogram (EGG). Investigational studies of gastric function include ultrasound, MRI and barostat measurements. The radionuclide gastric emptying study is the most commonly utilized test in the diagnosis of gastroparesis. Following the ingestion of a radiolabeled meal (typically eggs), the extent of gastric emptying is assessed at various time intervals. The results are usually expressed either as the percent of gastric retention or the t ½ of emptying. Since liquids are more easily emptied than solids, a solid phase emptying study must be performed when evaluating for gastroparesis. The techniques and analysis methods for radionuclide gastric emptying studies vary widely from institution to institution. This can lead to inaccuracies when comparing studies from different institutions and when following emptying rates over time. In an attempt to standardize this test, a multicenter study was performed on 123 normal persons utilizing a standard meal and analysis protocol .1 The meal consisted of eggbeater (60 kcal), two slices of bread (120 kcal), strawberry jam (75 kcal) and water (120 cc). The normal values obtained (expressed as percent gastric retention) were <90% retention at one hour, <60% retention at two hours and <10% retention at 4 hours. A four hour assessment is important because it has been demonstrated that up to 44% of patients who have a normal two-hour study may be abnormal at four-hours.
The most common cause of gastroparesis encountered in clinical practice is diabetic gastroparesis, which has been estimated to affect 20-40% of diabetic patients. Diabetic gastroparesis may be due to an autonomic (vagal) neuropathy, intrinsic neuropathy (interstitial cells of Cajal, excitatory and inhibitory nerves) and poor glucose control. These changes can lead to impaired fundic relaxation, abnormal electrical rhythms, reduced antral contractility and impaired pyloric opening. Hyperglycemia has been shown to worsen gastric emptying, therefore careful glucose control is vital in managing this condition. Many cases of gastroparesis are idiopathic in origin. Other etiologies for gastroparesis include post-viral syndrome, collagen vascular disorders, post-surgical conditions, Parkinson's disease, paraneoplastic syndrome and pseudoobstruction.
The treatment of gastroparesis in all patients begins with dietary management, and the cornerstone of dietary management is to eat smaller and more frequent meals. Fatty foods, fibrous foods, red meat and fresh vegetables should be avoided as these either delay gastric emptying or require significant trituration by the stomach. Protein and starches such as noodles, pasta, potatoes and rice are more easily mixed and emptied by the stomach. Liquid nutritional supplements may also be used. Medical therapy of gastroparesis includes anti-emetic agents, pro-motility drugs, visceral sensory modifiers and non-drug therapy. These are often used in combination since they exert their effects through different mechanisms. Endoscopic injection of Botox (100 U or 200 U) into the pyloric sphincter has been shown, in small uncontrolled series, to benefit some patients with gastroparesis.2,3 Although there are anecdotal reports of individual patients with dramatic responses, the overall results are disappointing and short-lived. The largest published report on Botox use for gastroparesis was a retrospective series by Bromer et al4 who reported on 63 patients (53 men, 10 women) who underwent injection of 100 or 200 U of Botox into the pylorus with a 23 gauge sclerotherapy needle. Twenty-seven patients (42.9%) achieved a symptomatic response, defined as improvement and/or resolution of their one major symptom or two or more of their minor symptoms for at least four weeks. The mean duration of the response was 5.2 months.
Fortunately, the vast majority of patients with gastroparesis can be managed with dietary changes and medical therapy. Approximately 5-15% of patients with gastroparesis who present to medical attention, however, may need nutritional support via a feeding jejunostomy or TPN. Surgical procedures intended to improve gastric emptying, such as a pylorplasty or gastrojejunostomy, have generally not been successful in managing these patients.5 For the rare patient who cannot tolerate J-feeds or TPN, a total gastrectomy can be considered.
Gastric electrical stimulation is a new technology that has been found to benefit some patients with severe gastroparesis. There are two main types of electrical stimulation that can be applied to the stomach. One is a low energy (300 µs pulse width), high frequency (12 cycles/minute) stimulation. The other is a high energy (300 ms pulse width), low frequency (3 cycles/minute) stimulation. The latter type of stimulator is known as a gastric pacemaker since it attempts to alter the basal electrical rhythm of the stomach in order to produce contractions. This type of device has had only limited investigation in humans.6 The low energy, high frequency device known as Enterra (Medtronics, Inc.) has been studied more extensively in humans and is FDA-approved as a humanitarian use device. This device is more appropriately referred to as a gastric electrical stimulator rather than a pacemaker. The primary effect of gastric electrical stimulation (GES) is unclear, but is likely related to neurostimulation-mediated activation of nausea and vomiting control mechanisms in the brain. Other possible effects of GES include augmentation of the gastric slow wave amplitude, enhanced relaxation of the proximal stomach and a small improvement in gastric emptying.7
The Enterra system consists of an implantable neurostimulator, two leads and an external, hand-held programmer. This device can be implanted via laparoscopy or open laparotomy. The two leads are attached with sutures to the muscularis propria of the stomach along the greater curvature of the antrum, while the stimulator is placed in a small pocket in the abdominal wall. The device is then set and activated in the operating room. Gastric electrical stimulation should be considered for patients with medically refractory gastroparesis who have severe and intractable symptoms, require frequent hospitalizations or are unable to maintain adequate nutritional status with oral intake. Typical exclusion criteria include pregnancy, chemical dependency, rumination syndrome, eating disorder, collagen vascular disease, cancer, paraneoplastic syndrome and peritoneal dialysis. Patients with post-surgical gastroparesis, previously excluded, are now considered potential candidates for GES.
Several studies have demonstrated the beneficial effects of GES in patients with gastroparesis. The GEMS study,8 published in 2002 reported on 38 patients (24 idiopathic, 9 diabetic, 5 post-surgical) with severe, drug-refractory gastroparesis who received GES. The patients were assessed at 3, 6 and 12 months after implantation of the stimulator. Thirty-five of 38 patients (97%) experienced a greater than 80% reduction in nausea and vomiting episodes. Gastric emptying did not change initially, but was improved in most patients at one year. Prior to GES, the median number of weekly episodes of nausea and vomiting was 21 for each symptom. At three months, the median number of episodes for each symptom decreased to less than one. This response was sustained at 6 and 12 months. The average weight gain was 5.5 lbs and 9/14 patients were able to discontinue TPN or enteral feeds. Complications included the removal of four stimulators due to infection and the removal of four stimulators for other reasons.
The WAVESS study (Worldwide Anti-Vomiting Electrical Stimulation Study), published in 2003,9 was a double-blind study that assessed the short-term effect of GES on symptom reduction as well as the long-term (12 months) effects on symptoms, gastric retention and health-related quality of life. The entry criteria were an abnormal gastric emptying study, symptoms present for more than 12 months, symptoms refractory to medical therapy and more than seven vomiting episodes per week. Thirty-three patients were enrolled, 17 with diabetic gastroparesis and 16 with idiopathic gastroparesis. In the diabetic group, the median number of vomiting episodes decreased from 13.4 episodes per week to 2.6 per week at 6 months (81% reduction) and 4.9 per week at 12 months (63% reduction). In idiopathic patients, the median number of vomiting episodes decreased from 26.8 episodes per week to 3.0 per week at 6 months (88% reduction) and 4.8 per week at 12 months (72% reduction). For the combined group, there was a significant reduction in gastric retention and significantly improved physical and mental well-being scores. Seventy-five percent of patients with J-tubes had the tubes removed by six months. The stimulator was removed in four patients due to infection, pain or erosion and was surgically repositioned in another patient. Based on the WAVESS data, the Enterra system was approved by the FDA under a humanitarian device exemption in 2000.
Several subsequent studies of GES have demonstrated statistically significant reductions in nausea and vomiting episodes, hospitalization frequency and the need for pro-kinetic drugs.10-12 A positive symptomatic response to GES is not necessarily associated with an improvement in gastric emptying. This strongly suggests that the beneficial response to GES is achieved through other mechanisms, as discussed earlier. One predictor of a positive clinical response to GES has been the presence of diabetic gastroparesis. Abell and colleagues15 have also demonstrated that the response to temporary GES, using electrodes placed on the inside of the stomach via a PEG or oral placement, can predict the response to permanent GES.
GES has also been shown to improve symptoms in patients with post-surgical gastroparesis.13,14 These procedures have included gastrojejunostomy, partial gastrectomy, vagotomy/pyloroplasty and Nissen fundoplication. McCallum et al14 implanted a stimulator in 16 patients with post-surgical gastroparesis and demonstrated significant improvements in upper GI symptoms, nutritional status and hospitalization requirements.
In summary, gastric electrical stimulation is an exciting and novel technique that dramatically improves symptoms, nutritional status and quality of life in some patients with refractory gastroparesis. Future research, along with a larger clinical experience with this device, will help identify the patients most likely to benefit from gastric electrical stimulation.
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