The Treatment of Gastroparesis in the Age of the Gastric Pacemaker: A Review

Daniel C. Buckles, MD, Jameson Forster, MD, Richard W. McCallum, MD

Disclosures
In This Article

Gastric Electrical Stimulation

Many patients with severe gastroparesis unfortunately do not achieve adequate relief from the previously outlined therapies. In such cases, consideration should be given to implantation of a gastric electrical stimulator. The only currently approved such device is manufactured under the trade name Enterra. At our Center for Gastrointestinal Nerve and Motor Function, approximately 50% of patients who are referred receive this modality. The device is approximately the size of a cardiac pacemaker and is implanted subcutaneously in the abdominal wall at the time of laparoscopy or laparotomy when electrodes are placed in the smooth muscle about 9.5-10 cm from the pylorus along the greater curvature of the antrum. The 2 electrodes are placed 1 cm apart, tangentially, deep in the muscularis propria and connected to the operating device. Intraoperative endoscopy is performed at the time of implantation to ensure that the leads are not accidentally pushed into the lumen of the stomach and are positioned appropriately in the muscularis propria of the stomach wall (Figures 2-4).

Figure 2.

GES stimulation system.

Figure 3.

GES implantation into abdominal wall.

Figure 4.

Abdominal radiograph of GES postoperatively.

The device delivers electrical stimuli to the stomach wall with a higher frequency (12 cpm) than the intrinsic gastric slow wave (2.5-3.5 cpm), but uses low-energy levels (300 microsec pulse width and 4-5 mA). Published reports indicate that this type of therapy leads to significant reductions in the frequency of nausea and vomiting. A study of 25 patients at our institution with gastroparesis (19 with diabetic gastroparesis) showed that this benefit was sustained at 12 months.[14] Weight gain of up to 8 pounds at 6 months and 15 pounds by 12 months was observed, and 79% of study participants had their jejunostomy tubes out by 6 months. Gastric emptying was not affected overall. However, 25% to 30% of patients did have normalization of their gastric emptying rate at 1 year. The most commonly seen complication has been pacemaker hardware infection requiring device removal. This has been observed in approximately 5% of patients, most of whom have longstanding diabetes.

The first double-blind trial was published in 2003 and involved 33 patients with idiopathic or diabetic gastroparesis.[28] This international, multicenter trial had a randomized, cross-over design with the device being on for 1 month, off for 1 month, and with follow-up for 12 months. Patients included in the study had symptoms of gastroparesis for more than 1 year, were drug-refractory, and had a vomiting frequency of more than 7 times per week. Gastric retention of a radionuclide-containing standardized, low-fat egg meal was abnormally slow at 2 and 4 hours after ingestion. The majority of these participants with gastroparesis were women and were white; the mean age in each group was approximately 40 years. Many of these patients had lost more than 10% of their body mass index and had been hospitalized frequently.

Results from this study showed significant reductions in the frequency of nausea and vomiting for the "on" vs "off" period, as well as sustained effects at 6 and 12 months for both the diabetic and idiopathic patient groups. Overall, 79% of patients had a 50% or greater decrease in vomiting. The benefits, as measured by total symptom score (ie, nausea, vomiting, bloating, fullness, satiety, and pain), were not as dramatic as for vomiting alone, but were still significant.

Open-label, uncontrolled studies performed at Kansas University Medical Center (KUMC) have shown additional positive outcomes associated with GES therapy.[28,29,30] Days of hospitalization were found to be reduced dramatically in gastroparetic patients treated with this therapy, from an average of 60 days per year to 17 days per year, post implantation. Additionally, the resulting estimated cost savings was $65,000 per patient after stimulator implant in the first year.[29] During the 1-year follow-up, many patients continued to eat smaller meals and generally needed prokinetic therapy for larger meals to address the gastric emptying component.[30] Furthermore, patients with diabetic gastroparesis also had the benefit of reduced hemoglobin A1c levels at 12 months.[31] The clinical benefits of GES therapy appear to be durable as well. A recent review found that patients followed for more than 24 months continued to have significant reductions in nausea and vomiting frequency when compared with baseline; this was accompanied by a decreased need for antiemetic and nutritional support (Buckles DC, Sarosiek I, Lin Z, et al, unpublished data, 2002) The majority of patients (87%) rated this therapy favorably and would choose it again.

Other data collected on the more than 100 patients who have undergone GES implantation at KUMC have contributed to our understanding of the pathogenesis of gastroparesis. It appears that one third of patients with idiopathic and diabetic gastroparesis have absent cells of Cajal on full-thickness gastric biopsies, and that these patients have increased abnormalities of gastric slow waves and a more severe symptom status, as well as a poorer outcome with GES therapy.[32]

In addition, we now have experience with gastroparesis in postvagotomy and presumed vagal nerve injury settings, including post-Nissen, vagotomy, and pyloroplasty, Billroth I and II, colonic interposition, and cervical vertebral surgery. Newer data on these patients (n = 12) have shown that nausea and vomiting and quality of life is improved by GES implantation.[33]

We are currently recommending GES therapy for patients who have had gastroparetic symptoms for more than 1 year and who are refractory to standard medical management and have abnormal gastric retention (at 2 hours over 60% and 4 hours over 10% as assessed using the standardized low-fat meal).[34] Patients with an organic obstruction or pseudo-obstruction, a primary eating or swallowing disorder, chemical dependency, or who are pregnant are not considered candidates for GES implantation. In view of the minimal effects on gastric emptying, other chronic nausea and vomiting states could be considered as settings for this device (eg, cyclic vomiting syndrome, renal failure, and chronic idiopathic nausea and vomiting).

In general, the effect of high-frequency/low-energy pacing on gastric contractility is unclear, as is the mechanism of action in decreasing symptomatology. Accelerations in gastric emptying times have been noted in some patients; however, this response is unpredictable and the majority of treated patients continue to have abnormal gastric emptying times after implantation. Furthermore, there has been poor correlation between the changes in symptoms and gastric emptying. In the WAVESS (Worldwide Anti-Vomiting Electrical Stimulation Study) trial,[28] 50% of patients normalized their gastric emptying times at 12 months, but there was no association between this observation and symptomatic improvement. This phenomenon has been demonstrated in earlier studies with prokinetic medications as well.[18,35,36,37] It has been hypothesized that the symptomatic improvement that has been observed is caused by modulation of enteric or afferent neural activity that influences symptom perception or that influences a central nausea and vomiting control mechanism.[38,39] Also, there have been recent reports that indicate that GES therapy changes various electrogastrography parameters, fundic relaxation, the autonomic nervous system, and gastrointestinal hormone levels.[40,41,42,43,44] These processes may also play some role in the effect of GES.

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