Gastric electrical stimulation in patients with gastroparesis

Abstract As in the heart, there is a pacemaker in the human stomach and it generates myoelectrical activity with a frequency of approximately three cycles per minute. Abnormalities in gastric myoelectrical activity may result in gastric motility disorders, such as gastroparesis. Electrical stimulation of the stomach is achieved by delivering electrical currents via electrodes attached to the smooth muscle of the stomach. Recently, a number of studies on electrical stimulation of the stomach in both humans and dogs have indicated that gastric electrical stimulation with appropriate parameters is able to entrain gastric slow waves and normalize gastric dysrhythmias. This has led some investigators to use gastric electrical stimulation to treat patients with gastroparesis. Previous studies and the current state of the field in gastric electrical stimulation in treatment of gastroparesis will be discussed and summarized.     

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.     

Treatment of high-frequency gastric electrical stimulation for gastroparesis

Background and Aims: The aim of this study was to assess the effects of gastric electrical stimulation (GES) on symptoms and gastric emptying in patients with gastroparesis, and the effects of GES on the three subgroups of gastroparesis. Methods: A literature search of clinical trials using high‐frequency GES to treat patients with gastroparesis from January 1995 to January 2011 was performed. Data on the total symptom severity score (TSS), nausea severity score, vomiting severity score, and gastric emptying were extracted and analyzed. The statistic effect index was weighted mean differences. Results: Ten studies (n = 601) were included in this study. In the comparison to baseline, there was significant improvement of symptoms and gastric emptying (P < 0.00001). It was noted that GES significantly improved both TSS (P < 0.00001) and gastric retention at 2 h (P = 0.003) and 4 h (P < 0.0001) in patients with diabetic gastroparesis (DG), while gastric retention at 2 h (P = 0.18) in idiopathic gastroparesis (IG) patients, and gastric retention at 4 h (P = 0.23) in postsurgical gastroparesis (PSG) patients, did not reach significance. Conclusions: Based on this meta‐analysis, the substantial and significant improvement of symptoms and gastric emptying, and the good safety we observed, indicate that high‐frequency GES is an effective and safe method for treating refractory gastroparesis. DG patients seem the most responsive to GES, both subjectively and objectively, while the IG and PSG subgroups are less responsive and need further research.     

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.     

Gastric electrical stimulation in intractable symptomatic gastroparesis

BACKGROUND: The treatment of gastroparesis remains unsatisfactory despite prokinetic and anti-emetic drugs. Gastric electrical stimulation has been proposed as a therapeutic option. We have assessed the effect of gastric electrical stimulation on symptoms, medical treatment, body weight and gastric emptying in patients with intractable symptomatic gastroparesis in a non-placebo-controlled study. METHODS: In this multicenter study, 38 highly symptomatic patients with drug-refractory gastroparesis were enrolled. Patients first received temporary electrical stimulation using percutaneous electrodes. The 33 responders to temporary stimulation then underwent surgical implantation of a permanent stimulator. Severity of vomiting and nausea was assessed before and after stimulation. Patients were reassessed 3, 6, and 12 months after permanent implantation. RESULTS: With stimulation, 35/38 patients (97%) experienced >80% reduction in vomiting and nausea. This effect persisted throughout the observation period (2.9-15.6 months, 341 patient-months). Gastric emptying did not initially change, but improved in most patients at 12 months. At 1 year, the average weight gain was 5.5% and 9/14 patients initially receiving enteral or parenteral nutrition were able to discontinue it. CONCLUSION: Electrical stimulation of the stomach has an immediate and potent anti-emetic effect. It offers a safe and effective alternative for patients with intractable symptomatic gastroparesis.     

Visceral response to acute retrograde gastric electrical stimulation in healthy human

AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity. METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography. RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude. The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals. CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.     

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 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.     

Gastric electrical stimulation for the treatment of diabetic gastroparesis

Diabetic gastroparesis is a component of autonomic neuropathy, and is the most common manifestation of gastrointestinal neuropathy. Diabetes is responsible for about one quarter of gastroparesis. The upper gastrointestinal symptoms are often non-specific and dominated by nausea, vomiting, early satiety, fullness, bloating. We also have to look for diabetic gastroparesis in case of metabolic instability, such as postprandial hypoglycaemia. The pathophysiology of diabetic gastroparesis is complex, partly due to a vagus nerve damage, but also to changes in secretion of hormones such as motilin and ghrelin. A decrease in the stem cell factor (SCF), growth factor for cells of Cajal (gastric pacemaker), was found in subjects with diabetic gastroparesis. These abnormalities lead to an excessive relaxation in the corpus, a hypomotility of antrum, a desynchronization antrum-duodenum-pylorus, and finally an abnormal duodenal motility. The treatment of diabetic gastroparesis is based on diabetes control, and split meals by reducing the fiber content and fat from the diet. The antiemetic and prokinetic agents should be tested primarily in people with nausea and vomiting. Finally, after failure of conventional measures, the use of gastric neuromodulation is an effective alternative, with well-defined indications. Introduced in the 1970s, this technology works by applying electrical stimulation continues at the gastric antrum, particularly in patients whose gastric symptoms are refractory to other therapies. Its efficacy has been recently reported in different causes of gastroparesis, especially in diabetes. Gastric emptying based on gastric scintigraphy, gastrointestinal symptoms, biological markers of glycaemic control and quality of life are partly improved, but not normalized. Finally, a heavy nutritional care is sometimes necessary in the most severe forms. The enteral route should be preferred (nasojejunal and jejunostomy if possible efficiency). However, in case of failure especially in patients with small bowel neuropathy, the long-term parenteral nutrition is sometimes required.     

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.     

短波胃电刺激对垂体后叶素所致呕吐样症状的作用

目的本文拟系统研究短脉冲和短波串脉冲胃电刺激对垂体后叶素所致犬呕吐样相关症状的作用。方法本文共研究了7条雌性Beagle犬,所有犬均于胃浆膜面埋植4对电极。实验随机分为4组。每组实验包括20分钟基础记录时间段、20分钟灌注垂体后叶素或盐水和另两个20分钟记录时间段。在1和2组中,盐水和垂体后叶素持续静脉滴注,不加胃电刺激。在3或4组中,垂体后叶素在第2个20分钟时间段灌注,胃电刺激(短脉冲:300μs,4mA,4IF;短波串脉冲:40Hz,6mA,0.3mswith3s开8s关)在前3个20分钟时间段中经由距幽门近端14cm处(第1对)电极给予。实验中记录胃慢波和呕吐样相关症状。结果①垂体后叶素能诱导胃电节律紊乱和呕吐样相关症状(ANOVA,P<0.001)。②短脉冲胃电刺激和短波串脉冲胃电刺激能减轻垂体后叶素所致呕吐样相关症状(P<0.001),但不能纠正胃电紊乱(P>0.05)。症状评分从垂体后叶素组14.7±1.4,减少至5.5±1.1(短脉冲胃电刺激组)和6.4±1.33(短波串脉冲胃电刺激组)。与垂体后叶素灌注不加电刺激比较(所有狗出现呕吐),短脉冲和短波串脉冲胃电刺激组中没有狗出现呕吐(P<0.001)。结论短脉冲和短波串脉冲胃电刺激能治疗呕吐样相关症状,而对胃电节律紊乱无作用。     

Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis

Management of gastroparesis remains challenging, particularly in pediatric patients. Supportive care and pharmacological therapies for symptoms remain the mainstay treatment. Although they are effective for mild and some moderately severe cases, often time they do not work for severe gastroparesis. There are a few prokinetics available, yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns. Currently, the only modality for adult patients with severe intractable gastroparesis is surgery, e.g., pyloroplasty and partial gastrectomy, however, this option is generally considered too radical for a growing child. Novel therapeutic approaches, particularly those which are less invasive, are needed. This article explores gastric electrical stimulation (GES), a new therapy for gastroparesis. Unlike others, it neither needs medications nor gastrectomy; rather, it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach. Thus, it is tolerated and safe in children. Like in adult patients, GES appears to work in releasing symptoms, improving nutrition, and enhancing the quality of life; it also helps wean off medications and eliminate many needs for hospitalization. Considering the transient nature of gastroparesis in children in many occasions, GES is considered a “bridging” therapy after failed medical interventions and before surgery.     

Serum gastrin response to food stimulation and gastric acid secretion in male patients with ileal resection.

Gastric acid secretion before and after stimulation with pentagastrin and serum gastrin response to a test meal were recorded in 9 male controls and in 7 male patients from whom more than 50 cm of the terminal ileum had been resected because of Crohn's disease. The mean gastric acid secretion before and after stimulation was not found to be significantly different in the two groups. The mean fasting serum gastrin concentration and the serum gastrin response in absolute values were not different in the two groups. The MAO-BAO/'integrated gastrin response' was higher (p less than 0.05), and the gastrin response in relation to fasting level was lower in the patients than in the controls (p less than 0.05). The results indicate that an increased parietal cell sensitivity to gastrin is present after ileal resection. The negative acid feed back mechanism, however, seems to be at work. Under physiological conditions, therefore, the increased sensitivity may not result in acid hypersecretion.