4What is Gastroparesis?A symptomatic chronic disorder of the stomach characterized by delayed gastric emptying in the absence of mechanical obstructionA stomach disorder in which food is digested more slowly than normal.In a healthy digestive system, strong muscular contractions move food from the stomach through the digestive tract.With gastroparesis, stomach muscles work poorly (or not at all), thus preventing the stomach from emptying properly.Steve: Needs to have the Parkman reference added
5SymptomsMost patients present with upper-gastrointestinal symptoms or with symptoms related to disordered gastric motor function. These include:Nausea and vomitingAbdominal bloatingAbdominal painFeelings of fullness after only a few bites of food (early satiety)Heartburn or gastroesophageal reflux disease (GERD)Changes in blood sugar levelsLack of appetiteExcessive weight lossSteve: Needs to have the Parkman reference added
6PrevalenceThe true prevalence of gastroparesis is not known; however, it has been estimated that up to 5 million persons in the US may suffer from this condition.*In a survey patients with documented chronic gastroparesis patients, it was found that the origins were about 36 percent idiopathic and 29 percent diabetic, with the remaining amount attributed to several other causes.*** Abell T, et al.. Nutrition in Clinical Practice 2006.** Soykan I, et al.Dig Dis Sci
7Enterra® TherapyEtiologies of Gastroparesis(Disease States)
8Etiologies In a study of 146 patients, the most common origins were: Idiopathic (35%)Diabetic (29%)Postsurgical (13%)Others: Parkinson’s disease, vascular disease, pseudo-obstructionSoykan I et al. Dig Dis Sci 1998.
9Idiopathic Gastroparesis Delayed gastric emptying without apparent cause or underlying abnormality may be the most common form of gastroparesisSymptoms fluctuate: patient may have episodes of pronounced symptoms interspersed with relatively symptom-free intervalsPatients are frequently young or middle-aged womenKendall, McCallum. Gastroenterology 1993.Parkman et al. Gastroenterology 2004.
10Idiopathic Gastroparesis Symptoms may resolve after months or even yearsPatients with a viral trigger tend to have slow resolution of their symptoms over several yearsPatients without a viral trigger tend to show less improvement over timeParkman et al. Gastroenterology 2004.
11Idiopathic Gastroparesis In a study of 146 patients, 52 patients had idiopathic gastroparesis:23% had sudden onset of symptoms after viral syndrome, suggesting a potential viral etiology48% had severe abdominal pain19% had gastroesophageal reflux disease and non-ulcerative dyspepsia23% had depression8% had onset post-cholecystectomySoykan I et al. Dig Dis Sci 1998,
12Diabetic Gastroparesis Gastroparesis is a recognized complication of diabetes mellitusPrimarily among patients with long-standing type 1 diabetes and other associated complicationsGastroparesis affects:40-50% of people with Type 1 diabetes30-40% of people with Type 2 diabetesParkman. Gastroenterology 2004.Diabetes Institute Foundation Website. 2005
13Diabetic Gastroparesis Likely to result from impaired neural control of gastric motility, possibly at the level of the vagus nerveProblems with blood glucose control may be the first indication that a diabetic patient is developing gastroparesisGastroparesis contributes to poor glycemic control because of unpredictable delivery of food into the duodenumDelayed gastric emptying with continued insulin administration may produce hypoglycemiaParkman. Gastroenterology 2004.
14Post-surgical* Gastroparesis Any surgery of the upper intestinal tract (esophagus, stomach or duodenum) may result in injury to the vagus nerve**Gastroparesis may occur as a complication of a variety of surgical procedures***Post-vagotomy - Most often peptic ulcer surgery with vagotomyPost-fundoplication - Complication of fundoplication to treat GERDPost-bariatric - Most commonly Roux-en-Y gastric bypass for obesityPost lung and heart-lung transplantation* Use of gastric electrical stimulation for post-surgical gastroparesis is not an approved indication for Enterra® Therapy.**American College of Gastroenterolgy Website***Parkman et al. Gastroenterology 2004.
16Scintigraphy is the gold standard DiagnosisHistory and physical examination to assess:Underlying medical conditionDuration, severity and frequency of symptomsAssessment for obstruction (X-ray, endoscope)Nuclear medicine study – 4 hour scinotography (gastric emptying test)Scintigraphy is the gold standardParkman et al. Gastroenterology 2004.Tougas ???
18Treatment PrinciplesConsiderations in developing patient treatment planReduce symptomsCorrect fluid, electrolyte and nutritional deficienciesGlycemic control for diabetic patientsIdentify and rectify underlying cause, if possibleParkman et al. Gastroenterology 2004
20Diet ModificationOral diet modifications should include adjustments in composition, consistency, size, and frequency of mealsPatients should be prescribed meals which are low in fat and fiber, in order toPromote gastric motilityReduce symptoms of nausea, vomiting and abdominal painIf solid foods are not tolerated, a liquid diet can be tried, supplemented with vitamins and mineralsKoch. Practical Gastroenterol 1997.Karras, Pfeifer. Curr Ther Endocrinol Ther 1997.
21Drug TherapyThe commonly used pharmacotherapy for gastroparesis has been a combination of prokinetic agents and antiemetics, such asMetoclopramideErythromycinCisapride (no longer on the market)Domperidone (not currently available in US)Side effects are common with both prokinetics and antiemeticsDrug therapy options are limited
22Drug Therapy Antiemetic agents for nausea and vomiting Phenothiazines commonly prescribedSerotonin receptor antagonistsSide effects common, including sedation and extrapyramidal effectsAntiemetic drugs act on peripheral and central neural structuresParkman et al. Gastroenterology 2004.
23Drug Therapy Prokinetic agents to increase GI motility Metoclopramide: side effects may restrict use in up to 30% of patientsErythromycin: side effects (nausea, vomiting) may mimic those of gastroparesisCisapride: only available under compassionate use/limited access programs due to link with cardiac arrhythmias and sudden deathProkinetic medications enhance gut contractility and promote the aboral movement of luminal contents. In the stomach, prokinetic agents increase antral contractility, correct gastric dysrhythmias, and improve antroduodenal coordination.
24Options for Drug-Refractory Patients Gastrostomy tubeFor venting or suctioning the stomachJejunostomy tubeFeeding tube inserted into the small intestineComplications include infection, tube dysfunction, and tube dislodgement.Parkman et al. Gastroenterology 2004.
25Options for Drug-Refractory Patients Surgical proceduresGastrectomy: Lower stomach is stapled or surgically removed; upper stomach is reattached to small intestinePyloroplasty: Widening of opening to small intestineGastrojejunostomy: Creating a passage between stomach and small intestineRoux-en-Y diversion: Gastric bypassParkman et al. Gastroenterology 2004.
26Options for Drug-Refractory Patients Total parenteral nutrition (TPN)Intravenous delivery of nutritionOften utilized as an end-stage option when nutrition is severely compromised and weight loss extensiveShould be temporary due to complication riskThe cost of TPN is at least ten times greater than enteral feeding, with some patients consuming over $200,000 annually in healthcare costs
27Options for Drug-Refractory Patients Gastric electrical stimulation (Enterra® Therapy) is a viable treatment option for patients with chronic, drug refractory nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology.Enterra Therapy uses mild electrical stimulation to stimulate the nerves of the stomach, possibly activating a nausea- and vomiting-control mechanism to relieve the symptoms of gastroparesis.Parkman et al. Gastroenterology 2004.
28Enterra® Therapy Overview Gastric Pacing vs. Neurostimulation U. S. Indication / CE MarkPatient SelectionEnterra System componentsSurgical ProcedureProgramming and Patient Management
29Make full life possible for patients with chronic nausea or vomiting secondary to gastroparesis when medication is not effective.
30Gastric Pacing vs. Neurostimulation Enterra® TherapyGastric Pacingvs. Neurostimulation
31Gastric Electrical Stimulation (GES) Two different typesLow-frequency/Long duration/High energy stimulation: “Gastric pacing”High-frequency/Short duration/Low energy stimulation: “Enterra Therapy”Physiological and clinical effects of GES are determined by specific pulse parameters and the position of electrodes.Soffer et al. Aliment Pharmacol Ther 2009:30;681.
32GES with Low-Frequency/Long-Duration Pulses: “Gastric pacing” Stimulation Frequency: Intrinsic Frequency (3x/min)Drives (entrains) the frequency of the smooth muscle slow wave (intrinsic), at the same frequency of the external stimulusHigh energy stimulationRequires multiple sets of electrodesNot FDA approved
33US & CE Mark Indications Enterra® TherapyUS & CE Mark Indications
34Enterra Therapy U.S. Indication “Enterra Therapy is indicated for the treatment of patients with chronic, intractable (drug-refractory) nausea and vomiting secondary to gastroparesis of diabetic or idiopathic origin.”Designated as Humanitarian Use Device (HUD) September 1999 by the FDA.Approved as Humanitarian Device Exemption (HDE) March 2000 by the FDA.
35Guidelines - Humanitarian Use Device (HUD) Designation Device to treat <4,000 patients/year with rare disorderSafe / probable benefit to patient outweighs risk of injury and/or illness from its useRequires Institutional Review Board (IRB) approval
36Humanitarian Device Exemption (HDE) HDE authorizes marketing of a HUDMust have HUD designationDevice company completes application for HDE
37Enterra Therapy CE Mark Indication Enterra Therapy is indicated for the treatment of patients with chronic, intractable (drug-refractory) nausea and vomiting secondary to gastroparesis.CE Mark granted August 2002
39Key Selection Criteria Idiopathic or diabetic gastroparesisChronic, severe vomiting or nauseaDrug-refractoryParkman et al. Gastroenterology 2004.
40Patient Selection Physician weighs all available treatment options Evaluate appropriate patientsEducate patient and family about therapy and expectationsDiscuss surgical procedure of Enterra Therapy with patient and familyDefine follow-up schedule and expectationsParkman et al. Gastroenterology 2004.
45Surgical Procedure Performed under general anesthesia Surgical procedure lasts 1-2 hoursLaparoscopyLaparotomyNeurostimulator activated in OR or anytime after implant based on the surgeon’s medical judgmentX-ray post-surgery to document initial lead positionEvaluate neurostimulator parameters before dischargeParkman et al. Gastroenterology 2004.
46Surgical ProcedureUsing laparotomy or laparoscopy, two intramuscular leads with electrodes are fixed to the muscle of the lower stomachThe leads are attached to the neurostimulatorLaparotomy (abdominal incision)Laparoscopy (abdominal visualization via an endoscope)Parkman et al. Gastroenterology 2004.
48ProgrammingPreparation: turn programmer on, place programming head on device boxPre-program following instructions technical manualCheck impedance and programming final amplitudeBegin stimulation
49DocumentationFill out the Device Tracking Registration Form and affix serial number stickers: one IPG and two leadsMail top copy to Medtronic in prepaid, self-addressed envelopeThis will ensure the patient receives a permanent ID card for the device and is registered with Medtronic in case any product or safety notice must be sentPlace two copies in the patient’s chartPlace printed parameters (pre-and post-implant) in the progress notes in the patient’s chart
50Patient Management Post-op Provide patient with information on:Post-op careFollow-up instructionsMake sure the patient receives the temporary registration card and the patient manual, which are provided in the neurostimulator package
51Patient Follow-Up Visit within one month Repeat visits: six months/PRN Evaluate symptoms, adverse effects and neurostimulator parametersBe attentive to any possible side effects
55Study Goals Investigate short-term effect of GES on symptom reduction Assess effectiveness of GES on symptoms, gastric retention and health-related quality of life over 12-month periodEvaluate adverse eventsAbell et al. Gastroenterology 2003.
56WAVESS Study (Worldwide Anti-Vomiting Electrical Stimulation Study) N = 33 patients with chronic gastroparesis(17 diabetic, 16 idiopathic)Design: 12 month study conducted in two phasesPhase I – two month randomized placebo-controlled double-blind cross-over trial, followed immediately by phase IIPhase II – 10 month open-labelDuration: July 1997 – March 1999Abell et al. Gastroenterology 2003.
57Study DesignPatients received gastric electrical stimulation for 12 monthsPatients randomized in double-blind crossover design to stimulation ON or OFF for 1-month periodsBlind broken; all patients programmed to stimulation ON and evaluated at 6 and 12 monthsAbell et al. Gastroenterology 2003.
58WAVESS: Study Design Multicenter double blind crossover March 14-15, 1997WAVESS: Study Design Multicenter double blind crossoverONRandomBaseline1/2Implant1/2OFFPhase IPhase II12612MonthsN = Patients17 diabetic16idiopathicAbell et al. Gastroenterology 2003.Study Initiation Meeting USA, Washington13
59WAVESS Outcomes RESULTS – VOMITING Median vomiting frequency significantly decreased from baselineDiabetic group:Decreased from 13.4 episodes/week to 2.6 at 6 months (81%) and 4.9 at 12 months (63%)Idiopathic group:Decreased from 26.8 episodes/week to 3.0 at 6 months (88%) and to 4.5 at 12 months (83%)Combined group:Decreased from 17.3 episodes/week to 2.6 at 6 months (85%) and 4.8 at 12 months (72%)Abell et al. Gastroenterology 2003.
60Outcomes as 12-month follow-up post-implant 12-Month Vomiting FrequencyOutcomes as 12-month follow-up post-implant% Reduction> 80%> 50%< 25%Diabetic (n=10)55%73%18%Idiopathic (n=13)54%85%15%All (n=23)52%79%17%Abell et al. Gastroenterology Aug;125(2):421-8
61Results: Quality of Life (QOL) Physical scores significantly improved from baseline:In diabetic, idiopathic and combined groups at six monthsIn diabetic and combined groups at 12 monthsMental scores significantly improved from baseline:In combined group at 6 and 12 monthsAbell et al. Gastroenterology 2003.
62SF-36 Results * p < .025 Physical Composite Score Mental Composite Score* p < .025Abell et al. Gastroenterology 2003.
63Mean Hospital Days Etiology Prior Surg Post Diabetic (n=8) 70.5 6.4 41.1Idiopathic (n=16)38.15.421.2All patients (n=24)48.95.727.8Prior = Hospital days in year prior to implant surgerySurg = Hospital days for implant surgeryPost = Hospital days in year after dischargeAbell et al. Gastroenterology 2003.
64Complications/Adverse Events System removed in four patients due to:Infection of neurostimulator pocket (two patients)Pain related to lead perforation of stomachErosion of neurostimulator through skinSurgery to reposition and re-anchor neurostimulator in one patient due to discomfort from system migrationAbell et al. Gastroenterology 2003.
65ConclusionsIn this group of 33 patients with long-term gastroparesis, gastric electrical stimulation:Significantly reduced vomiting frequency and upper GI symptomsSignificantly improved quality of lifeRepresents a major advance in the treatment of medically refractory gastroparesisAbell et al. Gastroenterology 2003.
66Enterra Therapy Reimbursement, Coding and Billing Coverage and payment is available and is dependent on individual insurance carriers.Medtronic Gastroenterology Economic Solutions has resources available to help with specific DRG, CPT, and ICD-9 CM codes.
67ReferencesAbell et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003, Aug;125(2):421-8.American College of Gastroenterology Website. Available at: Accessed Feb. 22, 2005.Baigrie RJ et al. Enteral versus parenteral nutrition after oesophagogastric surgery: a prospective ransomized comparison. Aust. N.Z. J. Surg 1996, 66:Fontana RJ, Barnett JL. Jejunostomy tube placement in refractory diabetic gastroparesis: a retrospective review. Am J Gastroenterology 1996, 91(10):Hornbuckle K, JL Barnett. The diagnosis and work-up of the patient with gastroparesis. J Clin Gastroenterol 2000, Mar;30(2):Karras PJ, Pfeifer MA. Diabetic gastrointestinal autonomic neuropathy. Curr Ther Endocrinol Metab 1997, 6:Kendall BJ, McCallum RW. Gastroparesis and the current use of prokinetic drugs. Gastroenterol 1993, 1(2):Koch KL. Gastroparesis: diagnosis and management. Article eight in the series. Practical Gastroenterol 1997, November. Pp
68References, ContinuedMcCallum RW. Clinical pharmacology forum: motility agents and the gastrointestinal tract. Am J Med Sci 1996, Jul;312(1):19-26McCallum RW. Review of current status of prokinetic agents in gastroenterology. American Journal of Gastroenterology :Parkman HP et al. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004 Nov;127(5):Parkman HP et al. American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis. Gastroenterology 2004 Nov;127(5):Soykan I et al. Demography, clinical characteristics, psychological and abuse profile, treatment and long term follow up of patients with gastroparesis. Dig Dis Sci 1998, 11:Tougas G et al. Assessment of Gastric Emptying Using a Low Fat Meal: Establishment of International Control Values. Am J Gastroenterology 2000, Jun;95(6):The Diabetes Institutes Foundation Website. Available at: Accessed Feb. 22, 2005.
69Enterra Therapy for Gastroparesis: Product technical manual must be reviewed prior to use for detailed disclosure.Indications: The Medtronic Enterra Therapy System for gastric electrical stimulation (GES) is indicated for use in the treatment of chronic, intractable (drug refractory) nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology.Contraindications: The Enterra Therapy System is contraindicated in patients whom the physician determines are not candidates for surgical procedures and/or anesthesia due to physical or mental health conditions. Do not use shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy (all now referred to as diathermy) on patients implanted with a neurostimulation system. Energy from diathermy can be transferred through the implanted system and can cause tissue damage at the location of the implanted electrodes, resulting in severe injury or death. Diathermy is further prohibited because it can also damage the neurostimulation system components resulting in loss of therapy, requiring additional surgery for system explantation and replacement.Warnings: This system has not been evaluated for pregnancy, pediatric use, or patients under the age of 18, or over the age of 70. Strong sources of electromagnetic interference (EMI) can result in serious injury, system damage, or operational changes to the system. Strong sources of EMI include MRI, electrocautery, radiofrequency (RF)/microwave ablation, external defibrillators, ultrasonic equipment, radiation therapy, and theft detectors. Patients on anticoagulation therapy may be at a greater risk for post-operative complications. The system may be affected by or adversely affect other implantable devices such as cardiac pacemakers and cardioverters/defibrillators. Rupture or piercing of the neurostimulator can result in severe burns. The use of non-Medtronic components with this system may result in damage to Medtronic components, loss of therapy, or patient injury. When possible, identify and treat any infections remote to the implant site prior to surgery. It is recommended that the neurostimulator implant site be irrigated with antibiotic solution during surgery and that IV antibiotics be administered perioperatively. Infections at the implant site almost always require the surgical removal of the implanted system. Avoid excess lead slack in the abdominal cavity. The lead can become entangled with or erode into the bowel, which may result in bowel obstruction, bowel perforation, intra-abdominal infection, bowel resection and may require system revision.Precautions: Clinicians and patients should follow programming guidelines and precautions provided in product manuals. Patients should avoid manipulating or rubbing the neurostimulator system components, which can cause component damage, skin erosion, or stimulation at the implant site. Patients should be detoxified from narcotics prior to implant so that the effects of stimulation can be properly assessed. Patients should avoid activities that may put undue stress on the implanted neurostimulation system components. Patients should not scuba dive below 10 meters of water or enter hyperbaric chambers above 2.0 atmosphere absolute (ATA). Electromagnetic interference, postural changes, and other activities may cause shocking or jolting.Adverse Events: Adverse events related to the system include infection, stomach wall perforation, migration/erosion of the neurostimulator, programming difficulty, undesirable change in stimulation, implant site pain, hemorrhage, hematoma, migration/dislodgement of the lead, extra-abdominal pain, seroma, concomitant muscle stimulation, allergenic or immune system response to implanted materials, loss of therapeutic effect, and gastrointestinal complications including upper and lower gastro-intestinal (GI) symptoms.Humanitarian Device: Authorized by Federal law for use in the treatment of chronic intractable (drug refractory) nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology. The effectiveness of this device for this use has not been demonstrated.For further information, please call Medtronic at and/or consult Medtronic’s website atUSA Rx Only. Rev 0709