Gastric electrical stimulation results in improved metabolic control in diabetic patients suffering from gastroparesis.

AIMS/HYPOTHESIS: Symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. Gastric electrical stimulation (GES) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. However, the effect of GES on metabolic control has not been assessed yet. METHODS: We performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy GES on symptoms, gastric emptying (measured scintigraphically), and metabolic control (HbA1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. RESULTS: Seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. No therapy-associated adverse events occurred. Weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. Gastric retention rates improved significantly from 83 % (2 h) and 38 % (4 h) to 35 % (2 h)/14 % (4 h) and 25 % (2 h)/17 % (4 h) at 6 and 12 months, respectively. HbA1c values were lowered in all 17 subjects; initially, all HbA1c values were above 7.5 %; at 6 and 12 months, mean values had significantly decreased from 8.6 % to 6.2 % and 6.5 %, respectively. CONCLUSIONS/INTERPRETATION: Gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. This study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by HbA1c, a surrogate marker of the risk of diabetic complications.     

Gastric electrical stimulation in medically refractory nausea and vomiting

INTRODUCTION: High-frequency gastric electrical stimulation is a new therapeutic option to improve refractory nausea and vomiting, in gastroparetic patients. Its effects on gastric emptying are, however, inconstant and limited. Therefore, we have hypothesized that high-frequency gastric electrical stimulation could be also effective in patients suffering from refractory vomiting and nausea with normal gastric emptying, and we have compared the symptomatic efficacy of high-frequency gastric electrical stimulation between patients with delayed and normal gastric emptying. PATIENTS AND METHODS: Fifteen patients with chronic, severe and medically resistant nausea and vomiting were included in the study. Gastric emptying was delayed in eight patients (Group 1) and normal in seven patients (Group 2). At inclusion and at 6 months after the start of the stimulation, symptoms (nausea and vomiting, bloating, regurgitations, abdominal pain and appetite) and quality of life were prospectively evaluated using the Gastrointestinal Quality of Life Index score whereas gastric emptying was assessed by scintigraphy and/or octanoic acid breath test. RESULTS: Age, sex, symptoms and quality of life were not different at baseline between the two groups. At 6 months, Gastrointestinal Quality of Life Index and nausea/vomiting scores had significantly improved in both groups. Other symptoms (bloating, regurgitations, abdominal pain and appetite) had improved at 6 months in Group 1 but not in Group 2. Six months after the start of stimulation, gastric emptying was normal in 4/8 Group 1 patients and 5/7 Group 2 patients but was not significantly different from that calculated before the implantation of the stimulator. CONCLUSION: Our results suggest that high-frequency gastric electrical stimulation could be an effective therapy for treating chronic, severe vomiting and nausea whether gastric emptying is delayed or not.     

Temporary gastric electrical stimulation with orally or PEG-placed electrodes in patients with drug refractory gastroparesis

BACKGROUND: Gastric electrical stimulation (GES) has been shown to be efficacious for drug refractory gastroparesis, but GES requires surgery. Placement of temporary GES electrodes endoscopically (ENDOstim) or via a PEG (PEGstim) is feasible, thereby allowing rapid assessment and comparison of temporary use (TEMP) with permanent (PERM) implantation. METHODS: Twenty consecutive patients with gastroparesis had TEMP electrodes placed (6 ENDOstim, 14 PEGstim). TEMP alone and TEMP vs. PERM placement of GES devices in 13 of 20 patients were compared via the following: average vomiting frequency score (VFS), total symptom score, days to symptom improvement, electrode impedance, and gastric emptying test. RESULTS: For patients receiving TEMP, GES demonstrated a rapid, significant, and sustained improvement in VFS, results similar to those for PERM. CONCLUSIONS: Both ENDO and PEG placement of GES electrodes are safe and effective in patients with gastroparesis, with outcomes that correspond to those achieved with permanent GES implantation.     

Gastric electrical stimulation in gastroparesis: where do we stand?

Gastroparesis is a chronic disabling condition of impaired gastric motility that results in decreased quality of life. Currently available medical therapy consists of prokinetic and/or antiemetic therapy, dietary modifications, and nutritional supplementation. For patients with medication-resistant gastroparesis a non-pharmacological therapy, gastric electric stimulation, has evolved over the last decade. Based on the frequency of the electrical stimulus, gastric electric stimulation can be classified into low- and high-frequency gastric electric stimulation. The first method aims to normalize gastric dysrhythmia and entrain gastric slow waves and accelerates gastric emptying, whereas high-frequency gastric electric stimulation is unable to restore normal gastric emptying, but nevertheless stunningly reduces symptoms, such as nausea and vomiting, re-establishes quality of life, nutritional state in all patients, and metabolic control in patients with diabetic gastroparesis. Gastric electric stimulation presents a new possibility in the treatment of gastroparesis.     

Gastroparesis： Current diagnostic challenges and management considerations

Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.     

Ischemic gastroparesis: resolution after revascularization

Patients with chronic nausea and vomiting frequently present challenging diagnostic and therapeutic problems. In such patients, gastroparesis of unknown cause, or "idiopathic" gastroparesis, may be the only objective finding. Two middle-aged women with nausea, vomiting, and weight loss of 10 and 26 kg over 6 and 18 months, respectively, were evaluated. Routine laboratory and barium study results were normal. Solid-phase gastric emptying studies showed severe gastroparesis in both patients. Upper endoscopies excluded gastric outlet obstruction. Gastric dysrhythmias (4-cpm and 1-cpm patterns) were recorded using cutaneous electrodes. An abdominal bruit was ascultated in one patient. Abdominal arteriograms in both patients showed total occlusion of all three major mesenteric vessels with collaterals supplied via hemorrhoidal arteries. Bypass grafting procedures of the celiac and superior mesenteric arteries in one patient and of the celiac artery in the other patient were performed. Six months after mesenteric artery revascularization, upper gastrointestinal symptoms had resolved and original weights were regained. Furthermore, normal 3-cpm gastric myoelectrical activity and normal gastric emptying of solids were restored in both patients. In these patients, chronic mesenteric ischemia resulted in a novel and reversible cause of gastroparesis, gastric dysrhythmias, and accompanying symptoms.     

Gastric emptying in patients with chronic renal failure receiving hemodialysis

Patients with renal failure requiring hemodialysis often suffer from nausea and vomiting. Gastric emptying has not been studied in these patients. To determine whether an abnormality of gastric emptying might account for symptoms in these patients, two groups of ten patients each were selected, one group with symptoms of nausea and vomiting and another without symptoms. Autonomic function was assessed in all patients. Fluid and solid gastric emptying rates were quantified utilizing a dual radionuclide technique. Half-emptying times for fluid and solid test meals were not statistically different from previous standards derived using the same methods in a normal population. Patients with chronic renal failure receiving hemodialysis have no demonstrable abnormality in gastric emptying, whether symptomatic or not.     

Gastric electrical stimulation for medically refractory gastroparesis

Background & aims:

This study investigated the efficacy of gastric electrical stimulation for the treatment of symptomatic gastroparesis unresponsive to standard medical therapy.

Methods:

Thirty-three patients with chronic gastroparesis (17 diabetic and 16 idiopathic) received continuous high-frequency/low-energy gastric electrical stimulation via electrodes in the muscle wall of the antrum connected to a neurostimulator in an abdominal wall pocket. After implantation, patients were randomized in a double-blind crossover design to stimulation ON or OFF for 1-month periods. The blind was then broken, and all patients were programmed to stimulation ON and evaluated at 6 and 12 months. Outcome measures were vomiting frequency, preference for ON or OFF, upper gastrointestinal tract symptoms, quality of life, gastric emptying, and adverse events.

Results:

In the double-blind portion of the study, self-reported vomiting frequency was significantly reduced in the ON vs. OFF period (P < 0.05) and this symptomatic improvement was consistent with the significant patient preference (P < 0.05) for the ON vs. OFF period determined before breaking the blind. In the unblinded portion of the study, vomiting frequency decreased significantly (P < 0.05) at 6 and 12 months. Scores for symptom severity and quality of life significantly improved (P < 0.05) at 6 and 12 months, whereas gastric emptying was only modestly accelerated. Five patients had their gastric electrical stimulation system explanted or revised because of infection or other complications.

Conclusions:

High-frequency/low-energy gastric electrical stimulation significantly decreased vomiting frequency and gastrointestinal symptoms and improved quality of life in patients with severe gastroparesis.     

Long term efficacy of gastric electrical stimulation in intractable nausea and vomiting

BackgroundAlthough the efficacy of gastric electrical stimulation has been reported in short-term studies, there is a lack of data on the long-term improvement of nausea and vomiting by gastric electrical stimulation in patients with delayed or normal gastric emptying.MethodsThirty-one patients were implanted at our centre for medically refractory severe and chronic nausea and/or vomiting. Patients were evaluated at baseline, 6 months then 5 years after implantation (mean follow-up 80 ± 4 months) using a symptomatic and quality of life scores.Key resultsAmongst the 31 patients, 4 were lost to follow-up, 6 explanted due to lack of improvement, and 1 patient died. Out of the 20 patients evaluated over 5 years, the quality of life score showed 27% improvement (p < 0.01), including nausea (62%; p < 0.01), vomiting (111%; p = 0.03), satiety (158%; p < 0.01), bloating (67%; p < 0.01) and epigastric pain (43%; p = 0.03). Over 5 years, 15/20 patients reported a 50% improvement with a global satisfaction rated at 64 ± 6%. Therefore, 15/27 patients (56%) were improved by gastric electrical stimulation over 5 years in intention to treat. Improvement of nausea 6 months after implantation was predictive of 5-year success of gastric electrical stimulation (p = 0.04). Finally, patients with delayed gastric emptying or with normal gastric emptying rate before surgery were similarly improved over 5 years (60% versus 50% respectively).ConclusionGastric electrical stimulation is safe and effective in the long term in patients with medically refractory nausea and vomiting, with an efficacy over 50% beyond 5 years in intention to treat. Gastric emptying measured before implantation did not influence the response rate over 5 years.     

Effect of metoclopramide in diabetic gastroparesis

The aims of our study were to: determine the effect of metoclopramide parenterally and orally on delayed gastric emptying of a radionuclide test meal in symptomatic patients with diabetic gastroparesis not explained by ulceration or other mechanical problems; and evaluate in a double-blind crossover fashion the efficacy of metoclopramide in relieving the symptoms of diabetic gastroparesis. Thirteen patients with subjective evidence of gastric stasis had delayed gastric emptying of an isotope-labeled semisolid meal which was significantly accelerated (p less than 0.05) after 10 mg of metoclopramide parenterally. Patients then received metoclopramide 10 mg and placebo before meals and prior to retiring for 3 weeks in a randomized double-blind crossover design. During metoclopramide therapy nausea, vomiting, anorexia, fullness, and bloating were significantly (p less than 0.05) ameliorated compared to placebo with an overall mean symptom reduction of 52.6%. Gastric emptying studies after completion of the trial is seven patients, subjectively improved and receiving open-labeled metoclopramide, showed significantly less gastric retention. Individual improvements in gastric emptying after parenteral or oral metoclopramide, however, could not be correlated with symptom change during the treatment trial. We conclude that metoclopramide is an important therapeutic adjunct in the management of diabetic gastroparesis and its therapeutic effects are mediated through its prokinetic properties as well as centrally mediated antiemetic actions.     

Rapid improvement in post-infectious gastroparesis symptoms with mirtazapine

We report the case of a 34-year-old woman with severe post-infectious gastroparesis who was transferred from an outside medical facility for a second opinion regarding management.This patient had no prior history of gastrointestinal symptoms.However,in the aftermath of a viral illness,she developed two months of intractable nausea,vomiting,and oral intake intolerance that resulted in numerous hospitalizations for dehydration and electrolyte disturbances.A solid-phase gastric emptying scan had confirmed delayed emptying,confirming gastroparesis.Unfortunately,conventional pro-kinetic agents and numerous anti-emetic drugs provided little or no relief of the patient’s symptoms.At our institution,the patient experienced a cessation of vomiting,reported a significant reduction in nausea,and toler-ated oral intake shortly after taking mirtazapine.Based on mirtazapine’s primary action as a serotonin(5-HT)1a receptor agonist,we infer that this receptor system mediated the clinical improvement through a combination of peripheral and central neural mechanisms.This report highlights the potential utility of 5-HT1a agonists in the management of nausea and vomiting.We conclude that mirtazapine may be effective in treating symptoms associated with non-diabetic gastroparesis that are refractory to conventional therapies.     

Gastric electric stimulation for the treatment of gastroparesis

Gastric electric stimulation is an emerging therapy for refractory gastroparesis. Several methods have been used to electrically stimulate the stomach. Initial studies used gastric electrical pacing, which entrains and paces the gastric slow waves at a slightly higher rate than the patient’s normal myoelectric frequency of 3 cycles per minute (cpm). The technique currently practiced uses high-frequency, low-energy stimulation at four times the basal rate (12 cpm). Results from published studies with high-frequency stimulation reveal an improvement in symptoms, primarily of nausea and vomiting, and primarily in patients with diabetic gastroparesis, with only a modest change in gastric emptying. As treatment with gastric electric stimulation evolves, further delineation of its overall effectiveness, the type of patient that will likely respond, optimal electrode placement(s), and stimulus parameters should be explored.     

Treatment of gastroparesis with electrical stimulation

Electrically stimulating the stomach to treat gastroparesis has been proposed by investigators for decades. With the development of techniques of implantable pacing devices and electrodes and promising preliminary results in chronic pacing studies, gastric electrical stimulation (GES) has received increasing attention recently among researchers and clinicians. A number of studies have been performed to investigate the effects of GES on gastric motility, gastric emptying, and gastrointestinal symptoms in both dogs and humans. Based on the frequency of the electrical stimulus used for chronic treatment of gastroparesis, gastric electrical stimulation can be classified into low-frequency stimulation (LFS) and high-frequency stimulation (HFS). Although some of the results are still controversial, the majority of these studies seem to indicate that LFS is able to normalize gastric dysrhythmias and entrain gastric slow waves and accelerate gastric emptying. On the other hand, HFS has no effect on gastric emptying but is able to significantly reduce symptoms of nausea and vomiting in gastroparetic patients. GES has provided an exciting new advance in the treatment of gastroparesis and management of upper gastrointestinal symptoms. This paper will review the available studies of GES in the treatment of gastroparesis and current status of this field.     

不同阶段糖尿病胃运动障碍诊治对策

糖尿病患者常见胃运动障碍,表现为上腹胀、早饱、上腹不适、恶心、呕吐等症状以及胃排空延迟,胃排空延迟影响降血糖药的药代动力学,造成餐后血糖升高与降血糖药或胰岛素的血浓度高峰不匹配,进而影响血糖的控制与稳定。糖尿病不同阶段胃运动障碍表现形式不同。核素法是最常用的胃排空诊断方法。糖尿病胃运动障碍的处理包括饮食调节、促动力药以减轻症状、控制血糖,针对胃轻瘫的治疗包括胃电刺激、内镜下幽门注射肉毒杆菌毒素A、内镜下放置鼻胃空肠营养管或经皮内镜下胃（空肠）造瘘、外科手术等。     

Minimally-invasive temporary gastric stimulation: A pilot study to predict the outcome of electronic gastric stimulation with the Enterra™ system

IntroductionGastroparesis (GP) is defined as delayed gastric emptying (GE) without any obstruction of the pylorus. It can be divided into idiopathic, diabetic, post surgical and rare causes. Electronic gastric stimulation (EGS) – Enterra Medtronic™ – is a part of GP therapy. Although its positive impact has been reported in open label trials, randomized controlled trials failed in demonstrating a positive outcome. The aim of this pilot study was to establish a reliable prediction for permanent gastric stimulation.Patients and procedure6 female patients underwent laparoscopic implantation of 2 temporary electrodes. The Enterra™ system was connected and taped to the skin. Baseline and postoperative gastroparesis cardinal symptom index (GCSI), a validated index for GP therapy, was assessed. Response to EGS was defined as a 50% decrease of baseline GCSI.Results4 of 6 patients responded to temporary EGS. 3 of 4 responders underwent permanent implantation. 1 non-responder received a permanent Enterra™ at another institution. After a median follow up time of 9 months the responder group GCSI remained low, whereas the non-responder GCSI had increased. Moreover, the health care system was saved € 30,678.03 by this test stimulation concept.ConclusionLaparoscopic implantation of a temporary EGS system predicts the outcome of permanent gastric stimulation and is cost-saving.     

The "electrical way" to cure gastroparesis

The treatment of gastroparesis recently received a heavy blow from the restrictions on the use of the prokinetic drug cisapride, but, fortunately, at the same time, a nonpharmacological approach, such as gastric electrical stimulation, came up again with new techniques. After an ultra-decennial experimentation with a large variety of electrical stimuli delivered to the gastric wall of animals and patients with gastroparesis, three principal methods are available at the moment: gastric electrical pacing, high-frequency gastric electrical stimulation, and sequential neural electrical stimulation. The first method aims to reset a regular slow-wave rhythm, but is unable to re-establish efficient contractions and a normal gastric emptying. High-frequency gastric electrical stimulation, although inadequate to restore a normal gastric emptying, nevertheless strikingly improves the dyspeptic symptoms, such as nausea and vomiting, giving the patients a better quality of life and a more satisfactory nutritional status. The last method, neural electrical gastric stimulation, consists of a microprocessor-controlled sequential activation of a series of annular electrodes which encircle the distal two thirds of the stomach and induce propagated contractions causing a forceful emptying of the gastric content. The latter method is the most promising, but it has so far only been tested in animals and would need to be tested in patients with gastroparesis before it can be used as a solution for this disease. All the aforementioned clinical studies, however, are not controlled and nearly all were published in abstract form. Therefore, further controlled trials are needed to establish which of these techniques is more useful for the treatment of gastroparesis.     

Efficacy of Gastric Electrical Stimulation in Improving Functional Vomiting in Patients with Normal Gastric Emptying

The objective of this study is to evaluate the utility of gastric electrical stimulation (GES) in the subgroup of patients with refractory nausea and vomiting in the presence of normal gastric emptying. Eighteen patients (15 females) underwent GES implantation for dyspeptic symptoms in the presence of normal gastric emptying. Upper gastrointestinal (UGI) symptom score, health-related quality of life (HR-QOL), nutritional status and weight, and medication use (prokinetics and antiemetics) were assessed at baseline and at 1 year after GES placement. Twelve patients (two males) were included in the final analysis. All patients had normal gastric emptying scintigraphy at baseline. After 1 year of GES, there was a significant reduction in the UGI symptom score from 18 to 10 (P = 0.001). The physical component score (PCS) of the HR-QOL was also significantly increased from 25 to 42 (P = 0.04). Gastric emptying actually became slower in 29% of those who repeated the test after 1 year. No adverse events related to GES placement were recorded. Results of our study suggest that GES improves dyspeptic symptoms in patients with medically refractory nausea and vomiting independent of its effect on gastric emptying and could be considered as a potential therapy in this clinical setting.     

Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.     

Clinical application prospects of gastric pacing for treating postoperative gastric motility disorders

Similar to the heartbeat, gastric peristalsis is regulated by an electrical rhythm generated by a pacemaker. Thus, electrical dysrhythmia of gastric slow waves will inevitably affect gastric peristalsis and emptying. The recurrence of postoperative gastroparesis is thereby closely related to the abnormalities of electrical dysrhythmia and ectopic pacemakers, resulting in postoperatively persistent gastric motility disorders in some severe cases, despite the use of prokinetic and antiemetic drugs. Recent studies have demonstrated that gastric pacing, analogous to pacing the human heart, is an attractive and promising therapy that is both feasible and safe. Gastric pacing has been shown to be strikingly effective in normalizing gastric dysrhythmia, increasing the activity of the gastric slow wave and thereby prompting gastric dynamia and emptying. Furthermore, the long-term utilization of gastric pacing can (i) relieve patients from clinical symptoms, such as nausea and vomiting; (ii) release patients with severe postoperative gastroparesis from relying on prokinetic drugs and the jejunal feeding tube; (iii) return patients to normal oral nutritional intake and provide a more satisfactory nutritional status and most importantly; and (iv) give patients a better quality of life. Overall, research focused on gastric pacing has demonstrated excellent prospects for clinical application in the treatment of postoperative gastroparesis disorders, especially for those unresponsive to prokinetic drugs.     

Gastric involvement in systemic sclerosis: a prospective study

OBJECTIVES: This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. METHODS: Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. RESULTS: The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. CONCLUSIONS: Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of < 1 on EGG and delayed gastric emptying). Gastric-emptying evaluation of radiopaque pellets may further be a helpful method to depict symptomatic SSc patients with gastroparesis. Finally, our series confirms that watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency.