Baseline predictive factors for foregut and hindgut response to long-term gastric electrical stimulation using augmented energy.

INTRODUCTION: Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. PATIENTS: We evaluated 307 patients at baseline, 1 week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation. METHODS: Foregut and hindgut PRO symptoms were analyzed for 12-month patient outcomes. All patients utilized a standardized energy algorithm with the majority of patients receiving medium energy at 12 months. Patients were categorized based on change in average GI symptom scores at the time of permanent GES compared to baseline using a 10% decrease over time as the cutoff between improvers versus non-improvers. RESULTS: By permanent GES implant, average foregut and hindgut GI symptom scores reduced 42% in improved patients (n = 199) and increased 27% in non-improved patients (n = 108). Low BMI, baseline infrequent urination score, mucosal EG ratio, and proximal mucosal EG low-resolution amplitude remained significant factors for improvement status. CONCLUSIONS: GES, for patients responding positively, improved both upper/foregut and lower/hindgut symptoms with most patients utilizing higher than nominal energies. Low baseline BMI and the presence of infrequent urination along with baseline gastric electrophysiology may help identify those patients with the best response to GES/bio-electric neuromodulation.

Gastric electrical stimulation optimized to inhibit gastric motility reduces food intake in dogs.

AIMS: The aim of this study was to test the hypothesis that that a method of gastric electrical stimulation (GES) optimized to inhibit gastric motility was effective in reducing food intake in dogs. METHODS: Female dogs with a gastric cannula and gastric serosal electrodes were studied in three experiments: (1) to determine the best parameters and locations of GES in inhibiting gastric tone, slow waves, and contractions in dogs;( 2) to investigate the reproducibility of the inhibitory effects of GES; and (3) to study the effect of the GES method on food intake in dogs. RESULTS: (1) For GES to exert significant effects on gastric motility, a pulse width of ≥2 ms was required, and with other appropriate inhibitory parameters, GES was able to increase gastric volume by 190.4 %, reduce antral contractions by 39.7 %, and decrease the percentage of normal slow waves by 47.6 %. In addition, the inhibitory effect of GES was more potent with the stimulation electrodes placed along the lesser or greater curvature than placed in the middle, and more potent with the electrodes placed in the distal stomach than in the proximal stomach; (2) the inhibitory effects of GES on gastric motility were reproducible; (3) the GES method optimized to inhibit gastric motility produced a 20 % reduction in food intakes in non-obese dogs. CONCLUSION: GES with appropriate parameters inhibits gastric motility, and the effects are reproducible. The GES method optimized to inhibit gastric motility reduces food intake in healthy dogs and may have a therapeutic potential for treating obesity.

Food intake and body weight responses to intermittent vs. continuous gastric electrical stimulation in diet-induced obese rats.

BACKGROUND: Gastric electrical stimulation (GES) has recently been introduced as a potential therapy for the treatment of obesity. The main challenge for the new generation of devices is to achieve desired clinical outcomes at a suitably low level of energy consumption. The aim of this study is to compare the effectiveness of GES with continuous and intermittent duty cycles in reducing food intake and body weight in diet-induced obesity-prone rats. METHODS: In macro duty cycle experiment, 40 rats were divided into groups to receive a sham GES, continuous GES, or intermittent GES (15 min On-45 min Off or 15 min On-15 min Off) for 28 days. In micro duty cycle experiment, 18 rats received cross-over treatment of continuous stimulation, 60 % time cycle or 40 % time cycle. Food intake, body weight, gastric emptying and ghrelin level were measured to evaluate the effect of different GES. RESULTS: GES with macro duty cycle intensity-dependently reduced mean daily food intake increase by 18.6, 10.2 and -6.0 % compared to 42.7 % with sham GES and body weight gain by 6.1 %, 3.4 and -0.8 % compared to 5 % with sham GES. Daily food intake decreased with increasing micro duty cycle intensity, averaging 16.5, 15.6 and 13.7 g/day under 40 % cycle, 60 % cycle and continuous stimulation respectively. Gastric emptying was intensity-dependently delayed by GES. GES has no effect in modulating plasma ghrelin level. CONCLUSIONS: GES energy-dependently reduces food intake, body weight and gastric emptying. Peripheral modulation of plasma ghrelin level is not related to the GES effects.

Gastric electrical stimulation is associated with improvement in pancreatic exocrine function in humans.

OBJECTIVE: To define the possible effects of gastric electrical stimulation (GES) for gastroparesis on pancreatic function, we performed 2 related human studies. METHODS: Fecal elastase values were compared in 2 patient groups: (1) GES devices ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to prokinetic medications, (2) positive response (RES) to medications, and (3) normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were compared by paired t tests and/or ANOVA and reported as mean +/- SE. RESULTS: Elastase was different for GES-ON and OFF (508.0 +/- 92.2 vs. GES-OFF 378.6 +/- 87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P = 0.07). HRV revealed a lower percentage of change with device ON versus OFF (44.2 +/- 5.5 vs. 48.5 +/- 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9 +/- 4.5 vs. 25.7 +/- 5.3, P < 0.05). CONCLUSIONS: GES improves exocrine pancreatic release, effects autonomic control, and improves GI symptoms, suggesting a possible role for GES in the treatment of pancreatic insufficiency associated with gastroparesis.

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.