Gastric Electrical Stimulation as a New Treatment Modality for Refractory Nausea and Vomiting with Normal Gastric Emptying.

Nausea and vomiting are cardinal symptoms affecting many patients with delayed or normal gastric emptying. The current therapies are very limited and less than optimal. Therefore, gastrointestinal symptoms persist despite using all the standard approaches for gastroparesis, functional dyspepsia, or unexplained nausea and vomiting. It is well established that gastric electrical stimulation (GES) is effective in reducing nausea and vomiting in gastroparesis, but there are essentially no data available that detail the efficacy of GES in symptomatic patients without gastroparesis. We present a unique case of a female patient diagnosed with functional dyspepsia, whose nausea and vomiting which were refractory to all standard therapies were successfully addressed with the implantation of a GES system.

Effectiveness of gastric electrical stimulation in gastroparesis: Results from a large prospectively collected database of national gastroparesis registries.

BACKGROUND: Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial. METHODS: We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups. KEY RESULTS: GES patients were clinically worse (40% severe vs. 18% for non-GES; P < .001); worse PAGI-QOL (2.2. vs. 2.6; P = .003); and worse GCSI total scores (3.5 vs. 2.8; P < .001). We observed improvements in 48-week GCSI total scores for GES vs. non-GES: improvement by ≥ 1-point (RR = 1.63; 95% CI = (1.14, 2.33); P = .01) and change from enrollment (difference = -0.5 (-0.8, -0.3); P < .001). When adjusting for patient characteristics, symptom scores were smaller and not statistically significant: improvement by ≥ 1-point (RR = 1.29 (0.88, 1.90); P = .20) and change from the enrollment (difference = -0.3 (-0.6, 0.0); P = .07). Of the individual items, the nausea improved by ≥ 1 point (RR = 1.31 (1.03, 1.67); P = .04). Patients with GCSI score ≥ 3.0 tended to improve more than those with score < 3.0. (Adjusted P = 0.02). CONCLUSIONS AND INFERENCES: This multicenter study of gastroparesis patients found significant improvements in gastroparesis symptoms among GES patients. Accounting for imbalances in patient characteristics, only nausea remained significant. Patients with greater symptoms at baseline improved more after GES. A much larger sample of patients is needed to fully evaluate symptomatic responses and to identify patients likely to respond to GES.

Management of cyclic vomiting syndrome in adults: Evidence review.

BACKGROUND: This evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults. METHODS: We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant? RESULTS: We found very low-quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co-morbid conditions and complementary therapies. CONCLUSIONS: This evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association.

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence-based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate-to-severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first-line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L-carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well-being and patient care outcomes.

Central and Peripheral Effects of Transcutaneous Acupuncture Treatment for Nausea in Patients with Diabetic Gastroparesis.

BACKGROUND/AIMS: Nausea, an unpleasant symptom of diabetic gastroparesis (DMGP), has been reported to be alleviated by needleless transcutaneous electrical acupuncture (TEA). Our study was designed to utilize electroencephalography (EEG) and electrogastrography (EGG) recordings to investigate the central and peripheral responses of TEA in the treatment of nausea in DMGP patients. METHODS: Eleven DMGP subjects underwent simultaneous EEG and EGG testing while grading the severity of nausea following 30-minute intervals of: (1) baseline, (2) visual stimulation (VS) to provoke more nausea, (3) active VS together with TEA, and (4) TEA alone, and a final 15-minute recording without any intervention. RESULTS: The nausea score was increased to 5.9 ± 1.5 with VS (P < 0.05, vs 3.5 ± 1.0 at baseline), then reduced to 3.5 ± 1.2 with VS plus TEA, and to 2.5 ± 1.3 with TEA alone, while it continued at a score of 2.9 ± 1.0 post TEA (all significant, P < 0.05, vs VS without TEA). The mean percentage of normal gastric slow waves was decreased to 60.0 ± 5.7% with VS (P < 0.05, vs 66.6 ± 4.5% at baseline), then improved to 69.2 ± 4.8% with VS plus TEA, and maintained at 70 ± 3.6% with TEA alone. During initial VS, EEG signals showed right inferior frontal activity as the prominent finding, but during VS with TEA, left inferior frontal activity predominated. CONCLUSIONS: In DMGP, TEA improves gastric dysrhythmia and ameliorates nausea. TEA treatment of nausea provoked by VS resulted in a change of dominance from right to left inferior frontal lobe activity. These data provide new understandings of peripheral and central mechanisms for nausea, and potential future directions for DMGP treatment approaches.

The Long-Term Efficacy and Safety of Pyloroplasty Combined with Gastric Electrical Stimulation Therapy in Gastroparesis.

INTRODUCTION: Gastroparesis is delayed gastric emptying without mechanical obstruction. Symptomatic improvement can be 50-60% with gastric electrical stimulation. To address delayed gastric emptying, pyloroplasty was added. This study examines the long-term efficacy and safety of simultaneous gastric electrical stimulator implantation and pyloroplasty. METHODS: In this prospective single-arm trial conducted from 2012 to 2015, 27 [23 females; mean age 43 (22-63)] gastroparesis patients who underwent simultaneous gastric electrical stimulator implantation with Heineke-Mikulicz pyloroplasty were studied. Six (25%) underwent simultaneous robot-assisted pyloroplasty and gastric electrical stimulator implantation. Diagnosis of gastroparesis was based on the 4-h gastric emptying test defined as >60% retention of isotope at 2 h and >10% at 4 h. Total symptom scores assessing severity of nausea, early satiety, bloating, vomiting, post-prandial fullness, and epigastric pain were obtained at baseline and at follow-up visits, ranging from 3 to 38 months (mean: 17). RESULTS: Follow-up data from 24 patients were available for analysis. There was 71% improvement in total symptom score on follow-up. Mean retention decreased by 29.6 and 48.7% at 2 and 4 h and gastric emptying was normalized in 60%. There were no post-surgical complications. CONCLUSIONS: Combination of gastric electrical stimulator and pyloroplasty significantly accelerated gastric emptying and improved gastroparesis symptoms. Combining these two surgical therapies improves both subjective and objective endpoints in drug refractory gastroparesis.

Surgical approaches to treatment of gastroparesis: gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.

Gastric electrical stimulation (GES) is neurostimulation; its mechanism of action is affecting central control of nausea and vomiting and enhancing vagal function. GES is a powerful antiemetic available for patients with refractory symptoms of nausea and vomiting from gastroparesis of idiopathic and diabetic causes. GES is not indicated as a way of reducing abdominal pain in gastroparetic patients. The need for introducing a jejunal feeding tube means intensive medical therapies are failing, and is an indication for the implantation of the GES system, which should always be accompanied by a pyloroplasty to guarantee accelerated gastric emptying.

Two-channel gastric pacing in patients with diabetic gastroparesis.

BACKGROUND: Our primary goals were to investigate the effects of two-channel gastric pacing on gastric myoelectrical activity, and energy consumption with the secondary intent to monitor gastric emptying and symptoms in patients with severe diabetic gastroparesis. METHODS: Four pairs of temporary pacing wires were inserted on the serosa of the stomach at the time of laparotomy to place the Enterra™ System in 19 patients with severe gastroparesis not responding to standard medical therapies. Two of the pairs were for electrical stimulation and the other two for recording. Five days after surgery the optimal pacing parameters for the entrainment of gastric slow waves in each patient were identified by serosal recordings. Two-channel gastric pacing was then initiated for 6 weeks using a newly developed external multi-channel pulse generator. Electrogastrogram (EGG), Total Symptom Score (TSS), and a 4-h gastric emptying test were assessed at baseline and after 6 weeks of active gastric pacing. Enterra™ device was turned OFF during the duration of this study. KEY RESULTS: Two-channel gastric pacing at 1.1 times the intrinsic frequency entrained gastric slow waves and normalized gastric dysrhythmia. After 6 weeks of gastric pacing, tachygastria was decreased from 15 ± 3 to 5 ± 1% in the fasting state and from 10 ± 2 to 5 ± 1% postprandially (P < 0.05), mean TSS was reduced from 21.3 ± 1.1 to 7.0 ± 1.5 (P < 0.05) and mean 4-h gastric retention improved from 42 to 28% (P = 0.05). CONCLUSIONS & INFERENCES: Two-channel gastric pacing is a novel treatment approach which is able to normalize and enhance gastric slow wave activity as well as accelerate gastric emptying in patients with diabetic gastroparesis with a goal safety profile.

Does grading the severity of gastroparesis based on scintigraphic gastric emptying predict the treatment outcome of patients with gastroparesis?

OBJECTIVES: The objectives of this study were as follows: (1) Whether gastric emptying is different between gastroparesis (GP) patients responding or not responding to standard medical therapy; (2) Identifying if mild, moderate, and severe degrees of gastroparesis based on the scintigraphic gastric emptying test (GET) can predict treatment responses for GP of diabetic (DM) and idiopathic (ID) origin. METHODS: A total of 165 patients (119 F) diagnosed with GP [126 (76%) DM, 39 (24%) ID etiology] failed medical treatment and required the gastric electrical stimulation (GES) device (GES group). In addition, 112 patients (89 F) [37 (33%) DM, 75 (67%) ID] with GP who symptomatically responded to medical therapies are the comparison group (MED GP). All patients underwent a standardized scintigraphic GET consisting of low-fat (2%) isotope labeled egg beaters meal of 250 kcal. We also analyzed the GET data to find cut-off points for different degrees of GP and identified mild (11-20% retention), moderate (21-35%), and severe gastroparesis (>35%) based on percent retention of isotope at 4 h. RESULTS: Overall gastric retention at 4 h was significantly greater in the GES group (45±1.9%) than MED GP (30±2%) (p<0.001). The distribution severity of the GET was different in GES-treated patients than MED treated (p<0.001). In the diabetics, 57% of GES patients retained >35% after 4 h (severe) similar to 43% in the DM MED group. However, 50% of the ID GES patients had retention>35% at 4 h significantly more than only 17% of ID MED GP. Significantly more ID patients who responded to medical therapy had mild gastroparesis and significantly more requiring GES had severe GET (p<0.05). CONCLUSIONS: (1) GET in patients whose GP symptoms were refractory to standard medical therapy and required GES was significantly slower than in GP patients whose symptoms responded to medical therapy. (2) Stratifying GET into mild, moderate, and severe degrees of gastric retention does not predict whether a medical or surgical approach will be better to control the symptoms of diabetic GP but does correlate with treatment for the idiopathic GP subgroup.

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.

Gastrointestinal electrical stimulation for treatment of gastrointestinal disorders: gastroparesis, obesity, fecal incontinence, and constipation.

Electrical stimulation of the gastrointestinal (GI) tract is an attractive concept. Since these organs have their own natural pacemakers, the electrical signals they generate can be altered by externally delivering electric currents by intramuscular, serosal, or intraluminal electrodes to specific sites in the GI tract. This article reviews the advances in electrical stimulation of the GI tract by describing various methods of GI electrical stimulation and their peripheral and central effects and mechanisms; updating the status of GI electrical stimulation in the clinical settings of gastroparesis, obesity, fecal incontinence, and constipation; and predicting future directions and developments of GI electrical stimulation technology and their areas of possible clinical applications.

Chronic gastric electrical stimulation for gastroparesis reduces the use of prokinetic and/or antiemetic medications and the need for hospitalizations.

To investigate the effect of chronic gastric electrical stimulation (GES) on the daily use of prokinetics and antiemetics, hospitalizations, total symptom score (TSS), SF-36 status for health-related quality of life (HQOL), and gastric emptying of a solid meal, we evaluated 37 gastroparetic patients preoperatively and 1 year after undergoing GES implant. Prokinetic and antiemetic use was significantly reduced. Of 27 patients on at least one prokinetic at baseline, 8 were off at 1 year. Twenty-six patients requiring antiemetics before surgery decreased to 17. Mean TSS was significantly reduced and the reduction for patients off medications was significantly better than for patients still on medications. Overall SF-36 scores for HQOL were significantly improved, and patients off antiemetics had a significantly higher HQOL score than for patients on antiemetics at 1 year. Hospitalizations decreased from 50 +/- 10 days for the year prior to GES therapy to 14 +/- 3 days (P < 0.05). However, gastric emptying was not significantly improved. Conclusions are as follows. (1) Chronic GES significantly reduced the use of prokinetic/antiemetic medications and the need for hospitalization in gastropraretic patients, whose clinical and quality of life outcomes also significantly improved. (2) These data provide evidence of the positive economic impact of this new therapy on long-term clinical outcomes in gastroparetic patients not responding to standard medical therapy.

Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis.

BACKGROUND & AIMS: The aim of this study was to report the long-term clinical response to high-frequency gastric electrical stimulation (GES) in 16 patients with postsurgical gastroparesis who failed standard medical therapy. METHODS: Clinical data collected at baseline and after 6 and 12 months of GES included (1) severity and frequency of 6 upper gastrointestinal (GI) symptoms by using a 5-point symptom interview questionnaire and total symptom score, (2) health-related quality of life including physical composite score and mental composite score, (3) 4-hour standardized gastric emptying of a solid meal by scintigraphy, and (4) nutritional status. RESULTS: The severity and frequency of all 6 upper GI symptoms, total symptom score, physical composite score, and mental composite score were significantly improved after 6 months and sustained at 12 months ( P < .05). All patients had delayed gastric emptying at baseline. Gastric emptying was not significantly faster at 12 months, although 3 normalized. At implantation, 7 of 16 patients required nutritional support with a feeding jejunostomy tube; after GES, 4 were able to discontinue jejunal feeding. The mean number of hospitalization days was significantly reduced by a mean 25 days compared with the prior year. One patient had the device removed after 12 months because of infection around the pulse generator. CONCLUSIONS: Long-term GES significantly improved upper GI symptoms, quality of life, the nutritional status, and hospitalization requirements of patients with postsurgical gastroparesis. Although vagal nerve damage or disruption was part of the underlying pathophysiology, GES therapy was still effective and is a potential treatment option for the long-term management of postsurgical gastroparesis. A controlled clinical trial of GES for PSG patients (who are refractory to medical therapy) is indicated given these encouraging results.

Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings.

The interstitial cells of Cajal (ICCs) are fundamental in the generation of gastric slow waves. The role of these cells in gastroparesis has not been established. We studied 14 gastroparetic patients (9 diabetic, 4 idiopathic, and 1 postsurgical) for whom standard medical therapy had failed and who had been treated with a gastric electrical stimulator for at least 3 months. All patients had a full-thickness antral gastric wall biopsy at the time of surgery. The biopsy samples were stained with c-kit and scored for the presence of ICCs. Baseline electrogastrogram recordings were obtained for 30 minutes in the fasting state and for 2 hours after a test meal. The patients assessed their total symptom score at baseline and at 3 months. Five patients had almost no ICCs and were compared with nine patients with 20% to normal cell numbers. Both groups did respond symptomatically to gastric electrical stimulation. However, patients with depleted ICCs had significantly more tachygastria and had significantly greater total symptom scores at baseline and after 3 months of gastric electrical stimulation. ICCs are absent in some patients (up to a third) with diabetic or idiopathic gastroparesis, and the absence of these cells is associated with abnormalities of gastric slow waves, worse symptoms, and less improvement with gastric electrical stimulation.

Treatment of diabetic gastroparesis by high-frequency gastric electrical stimulation.

OBJECTIVE: To investigate the long-term efficacy of high-frequency gastric electrical stimulation (GES) for treating diabetic gastroparesis. RESEARCH DESIGN AND METHODS: This is a retrospective review of 48 adult diabetic patients with refractory gastroparesis who had a GES system implanted surgically and had follow-up evaluations at 6 and 12 months. The outcome measures were total symptom score (TSS), derived from six upper gastrointestinal (GI) symptom subscores; health-related quality of life (HQOL), including physical composite score (PCS) and mental composite score (MCS) assessed by SF-36 questionnaire, radionuclide gastric emptying test, nutritional status, HbA1c, and adverse events. RESULTS: In comparison with baseline, TSS, all six upper GI symptom subscores, PCS, and MCS were significantly improved at 6 months, with the improvement sustained at 12 months. Of 13 patients receiving nutritional support at baseline by tube feeding, only 5 required supplemental enteral feeding at 12 months, and none of the 9 on total parenteral nutrition continued this support. The mean number of hospitalization days during the year after GES was significantly reduced by 52 days compared with the prior year. HbA1c levels were significantly reduced at 12 months. Gastric emptying was only minimally and not significantly faster. Because of infections at the pulse generator pocket site, four patients had their GES systems removed 3-17 months postsurgery. CONCLUSIONS: In diabetic patients with refractory gastroparesis, high-frequency GES by a permanently implanted system significantly improved upper GI symptoms, HQOL, nutritional status, glucose control, and hospitalizations with an acceptably low complication rate.

Further experience with gastric stimulation to treat drug refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) has been introduced for patients with gastroparesis refractory to pharmacological therapy. METHODS: From April 1998 until November 2001, 55 patients underwent GES implantation at Kansas University Medical Center. All patients had prolonged gastric retention of a solid meal by scintigraphy at baseline. The etiologies were diabetes mellitus in 39, related to previous surgery in 9, and idiopathic in 7. Symptoms were graded using a 5-point scale and quality of life was assessed with the SF-36 questionnaire. Body mass index and nutritional parameters were monitored. Hemoglobin A1C was measured in the diabetic patients. RESULTS: Total symptom scores and the physical and mental composite scores of quality of life improved significantly. On average, gastric emptying did not change. Body mass index and body weight increased significantly. And days spent in hospital admissions were significantly decreased. At 1 year, diabetic patients experienced reduced hemoglobin A1C. Four devices were removed. One patient died of a pulmonary embolus postoperatively. CONCLUSIONS: In a large series of patients with gastroparesis, GES significantly improved symptoms and quality of life.

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.