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Enterra® Therapy
Overview
Enterra® Therapy
Defining Gastroparesis
Anatomical Overview
3
What is Gastroparesis?
– A symptomatic chronic disorder of the stomach
characterized by delayed gastric emptying in the absence
of mechanical obstruction
– A 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.
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Symptoms
Most patients present with upper-gastrointestinal symptoms or
with symptoms related to disordered gastric motor function.
These include:
– Nausea and vomiting
– Abdominal bloating
– Abdominal pain
– Feelings of fullness after only a few bites of food (early
satiety)
– Heartburn or gastroesophageal reflux disease (GERD)
– Changes in blood sugar levels
– Lack of appetite
– Excessive weight loss
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Prevalence
• The 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. 1998.
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Enterra® Therapy
Etiologies of
Gastroparesis
(Disease States)
Etiologies
In a study of 146 patients, the most common origins were:
–
–
–
–
Idiopathic (35%)
Diabetic (29%)
Postsurgical (13%)
Others: Parkinson’s disease, vascular disease, pseudo-obstruction
4%
6%
Idiopathic - 35%
5%
Diabetic - 29%
35%
8%
Post-surgical - 13%
Parkinson's - 8%
Vascular Disease - 5%
13%
Pseudo-obstruction - 4%
Miscellaneous - 6%
29%
Soykan I et al. Dig Dis Sci 1998.
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Idiopathic Gastroparesis
Delayed gastric emptying without apparent cause or
underlying abnormality may be the most common form of
gastroparesis
Symptoms fluctuate: patient may have episodes of
pronounced symptoms interspersed with relatively symptomfree intervals
Patients are frequently young or middle-aged women
Kendall, McCallum. Gastroenterology 1993.
Parkman et al. Gastroenterology 2004.
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Idiopathic Gastroparesis
Symptoms may resolve after months or even years
– Patients with a viral trigger tend to have slow resolution of
their symptoms over several years
– Patients without a viral trigger tend to show less
improvement over time
Parkman et al. Gastroenterology 2004.
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Idiopathic 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 etiology
48% had severe abdominal pain
19% had gastroesophageal reflux disease and nonulcerative dyspepsia
23% had depression
8% had onset post-cholecystectomy
Soykan I et al. Dig Dis Sci 1998,
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Diabetic Gastroparesis
Gastroparesis is a recognized complication of diabetes mellitus
–
Primarily among patients with long-standing type 1
diabetes and other associated complications
Gastroparesis affects:
–
40-50% of people with Type 1 diabetes
–
30-40% of people with Type 2 diabetes
Parkman. Gastroenterology 2004.
Diabetes Institute Foundation Website. 2005
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Diabetic Gastroparesis
Likely to result from impaired neural control of gastric motility,
possibly at the level of the vagus nerve
Problems with blood glucose control may be the first
indication that a diabetic patient is developing gastroparesis
– Gastroparesis contributes to poor glycemic control
because of unpredictable delivery of food into the
duodenum
– Delayed gastric emptying with continued insulin
administration may produce hypoglycemia
Parkman. Gastroenterology 2004.
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Post-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 vagotomy
Post-fundoplication - Complication of fundoplication to treat GERD
Post-bariatric - Most commonly Roux-en-Y gastric bypass for obesity
Post 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. 2005
***Parkman et al. Gastroenterology 2004.
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Enterra® Therapy
Diagnosing Gastroparesis
Diagnosis
• History and physical examination to
assess:
– Underlying medical condition
– Duration, severity and frequency of symptoms
– Assessment for obstruction (X-ray, endoscope)
• Nuclear medicine study – 4 hour
scinotography (gastric emptying test)
Scintigraphy is the gold standard
Parkman et al. Gastroenterology 2004.
Tougas ???
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Enterra® Therapy
Gastroparesis
Treatment Continuum
Treatment Principles
Considerations in developing patient treatment plan
• Reduce symptoms
• Correct fluid, electrolyte and nutritional deficiencies
– Glycemic control for diabetic patients
• Identify and rectify underlying cause, if possible
Parkman et al. Gastroenterology 2004
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Traditional Management
Treatment Continuum
Diet modification
Least invasive
Drug therapies
Enterra
Therapy
Enteral feeding / TPN
Surgical procedures
Total parental nutrition
Most invasive
Kendall, McCallum. Gastroenterology 1993.
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Diet Modification
Oral diet modifications should include adjustments
in composition, consistency, size, and frequency of
meals
Patients should be prescribed meals which are low
in fat and fiber, in order to
– Promote gastric motility
– Reduce symptoms of nausea, vomiting and abdominal pain
If solid foods are not tolerated, a liquid diet can be
tried, supplemented with vitamins and minerals
Koch. Practical Gastroenterol 1997.
Karras, Pfeifer. Curr Ther Endocrinol Ther 1997.
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Drug Therapy
The commonly used pharmacotherapy for
gastroparesis has been a combination of
prokinetic agents and antiemetics, such as
–
–
–
–
Metoclopramide
Erythromycin
Cisapride (no longer on the market)
Domperidone (not currently available in US)
Side effects are common with both prokinetics and
antiemetics
Drug therapy options are limited
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Drug Therapy
Antiemetic agents for nausea and vomiting
– Phenothiazines commonly prescribed
– Serotonin receptor antagonists
Side effects common, including sedation
and extrapyramidal effects
Parkman et al. Gastroenterology 2004.
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Drug Therapy
Prokinetic agents to increase GI motility
– Metoclopramide: side effects may restrict use in up to
30% of patients
– Erythromycin: side effects (nausea, vomiting) may
mimic those of gastroparesis
– Cisapride: only available under compassionate
use/limited access programs due to link with cardiac
arrhythmias and sudden death
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Options for Drug-Refractory Patients
Gastrostomy tube
– For venting or suctioning the stomach
Jejunostomy tube
– Feeding tube inserted into the small intestine
Complications include infection, tube dysfunction,
and tube dislodgement.
Parkman et al. Gastroenterology 2004.
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Options for Drug-Refractory Patients
Surgical procedures
– Gastrectomy: Lower stomach is stapled or surgically
removed; upper stomach is reattached to small intestine
– Pyloroplasty: Widening of opening to small intestine
– Gastrojejunostomy: Creating a passage between
stomach and small intestine
– Roux-en-Y diversion: Gastric bypass
Parkman et al. Gastroenterology 2004.
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Options for Drug-Refractory Patients
Total parenteral nutrition (TPN)
– Intravenous delivery of nutrition
• Often utilized as an end-stage option when nutrition is severely
compromised and weight loss extensive
– Should be temporary due to complication risk
• The cost of TPN is at least ten times greater than enteral
feeding, with some patients consuming over $200,000 annually
in healthcare costs
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Options 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.
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Enterra® Therapy
Overview
•
•
•
•
•
•
Gastric Pacing vs.
Neurostimulation
U. S. Indication / CE Mark
Patient Selection
Enterra System components
Surgical Procedure
Programming and Patient
Management
Make full life
possible for patients
with chronic nausea
or vomiting
secondary to
gastroparesis
when medication
is not effective.
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Enterra® Therapy
Gastric Pacing
vs. Neurostimulation
Gastric Electrical Stimulation (GES)
Two different types
1. Low-frequency/Long duration/High energy
stimulation: “Gastric pacing”
2. 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.
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GES 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 stimulus
• High energy stimulation
• Requires multiple sets of electrodes
• Not FDA approved
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Enterra® Therapy
US & CE Mark Indications
Enterra 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.
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Guidelines - Humanitarian Use
Device (HUD) Designation
Device to treat <4,000 patients/year with
rare disorder
Safe / probable benefit to patient outweighs risk
of injury and/or illness from its use
Requires Institutional Review Board (IRB)
approval
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Humanitarian Device Exemption (HDE)
HDE authorizes marketing of a HUD
– Must have HUD designation
– Device company completes application
for HDE
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Enterra 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
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Enterra® Therapy
Patient Selection
Key Selection Criteria
Idiopathic or diabetic gastroparesis
Chronic, severe vomiting or nausea
Drug-refractory
Parkman et al. Gastroenterology 2004.
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Patient Selection
• Physician weighs all available treatment options
• Evaluate appropriate patients
• Educate patient and family about therapy and
expectations
• Discuss surgical procedure of Enterra Therapy
with patient and family
• Define follow-up schedule and expectations
Parkman et al. Gastroenterology 2004.
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Enterra® Therapy
System Components
Gastric Electrical Stimulation (Enterra Device)
Neurostimulator
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Enterra System Components
Programmer
Pulse Generator &
Leads
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Enterra® Therapy
Surgical Procedure
Surgical Procedure
• Performed under general anesthesia
• Surgical procedure lasts 1-2 hours
– Laparoscopy
– Laparotomy
• Neurostimulator activated in OR or anytime
after implant based on the surgeon’s medical
judgment
• X-ray post-surgery to document initial lead
position
• Evaluate neurostimulator parameters before
discharge
Parkman et al. Gastroenterology 2004.
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Surgical Procedure
Using laparotomy or laparoscopy, two
intramuscular leads with electrodes are fixed to
the muscle of the lower stomach
The leads are attached to the neurostimulator
– Laparotomy (abdominal incision)
– Laparoscopy (abdominal visualization via an endoscope)
Parkman et al. Gastroenterology 2004.
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Enterra® Therapy
Programming &
Patient Management
Programming
• Preparation: turn programmer on, place
programming head on device box
• Pre-program following instructions technical
manual
• Check impedance and programming final
amplitude
• Begin stimulation
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Documentation
• Fill out the Device Tracking Registration Form
and affix serial number stickers: one IPG and
two leads
• Mail top copy to Medtronic in prepaid, selfaddressed envelope
– This 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 sent
• Place two copies in the patient’s chart
• Place printed parameters (pre-and post-implant)
in the progress notes in the patient’s chart
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Patient Management Post-op
Provide patient with information on:
– Post-op care
– Follow-up instructions
Make sure the patient receives the temporary
registration card and the patient manual, which are
provided in the neurostimulator package
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Patient Follow-Up
Visit within one month
Repeat visits: six months/PRN
Evaluate symptoms, adverse effects and
neurostimulator parameters
Be attentive to any possible side effects
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Enterra® Therapy
Clinical Studies
WAVESS Study
(Worldwide AntiVomiting Electrical
Stimulation Study)
Gastric Electrical
Stimulation for
Medically Refractory
Gastroparesis
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Study 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 period
Evaluate adverse events
Abell et al. Gastroenterology 2003.
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WAVESS Study
(Worldwide Anti-Vomiting Electrical
Stimulation Study)
N = 33 patients with chronic gastroparesis
(17 diabetic, 16 idiopathic)
Design: 12 month study conducted in two
phases
Phase I – two month randomized placebo-controlled doubleblind cross-over trial, followed immediately by phase II
Phase II – 10 month open-label
Duration: July 1997 – March 1999
Abell et al. Gastroenterology 2003.
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Study Design
Patients received gastric electrical stimulation for
12 months
– Patients randomized in double-blind crossover design to
stimulation ON or OFF for 1-month periods
– Blind broken; all patients programmed to stimulation ON
and evaluated at 6 and 12 months
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Abell et al. Gastroenterology 2003.
WAVESS: Study Design
Multicenter double blind crossover
ON
R
Baseline
a
n
d
Implant o
m
1/2
1/2
OFF
Phase I
0
N = 33
Phase II
1
2
33
33
6
12
Months
27
24
Patients
17 diabetic
16idiopathic
Abell et al. Gastroenterology 2003.
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WAVESS Outcomes
Vomiting frequency reduction
30
33, 17, 16
33, 17, 16
33, 17, 16
27, 13, 14
24, 11, 13
n
Episodes / Week
25
20
15
All
Diabetic
Idiopathic
*
* *
10
* *
*
* p < 0.05 vs .
bas eline
p < 0.05 on vs . off
5
0
Bas eline
OFF (1m th)
ON (1m th)
6 m ths
12 m ths
Mean
HQOL SF-36 Score Improve ments (All patie nts)
90
80
70
60
50
40
30
20
10
0
*
*
*
*
*
*
US norm s
12 m ths
Bas eline
*
* p < 0.005
n = 24
PF
RP
BP
GH
VT
SF
RE
MH
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Abell et al. Gastroenterology 2003.
12-Month Vomiting Frequency
Outcomes 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. 2003 Aug;125(2):421-8
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Results: Quality of Life (QOL)
Physical scores significantly improved from
baseline:
– In diabetic, idiopathic and combined groups at six
months
– In diabetic and combined groups at 12 months
Mental scores significantly improved from
baseline:
– In combined group at 6 and 12 months
Abell et al. Gastroenterology 2003.
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SF-36 Results
Physical Composite Score
Mental Composite Score
* p < .025
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Abell et al. Gastroenterology 2003.
Mean Hospital Days
Etiology
Prior
Surg
Post
Diabetic (n=8)
70.5
6.4
41.1
Idiopathic (n=16)
38.1
5.4
21.2
All patients (n=24)
48.9
5.7
27.8
Prior = Hospital days in year prior to implant surgery
Surg = Hospital days for implant surgery
Post = Hospital days in year after discharge
Abell et al. Gastroenterology 2003.
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Complications/Adverse Events
System removed in four patients due to:
– Infection of neurostimulator pocket (two patients)
– Pain related to lead perforation of stomach
– Erosion of neurostimulator through skin
Surgery to reposition and re-anchor
neurostimulator in one patient due to
discomfort from system migration
Abell et al. Gastroenterology 2003.
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Conclusions
In this group of 33 patients with long-term
gastroparesis, gastric electrical stimulation:
– Significantly reduced vomiting frequency and upper GI
symptoms
– Significantly improved quality of life
– Represents a major advance in the treatment of medically
refractory gastroparesis
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Abell et al. Gastroenterology 2003.
Enterra 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.
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References
•
Abell et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003,
Aug;125(2):421-8.
•
American College of Gastroenterology Website. Available at:
http://www.acg.gi.org/patients/gihealth/gastroparesis.asp. 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, 66:668-670.
•
Fontana RJ, Barnett JL. Jejunostomy tube placement in refractory diabetic gastroparesis: a retrospective
review. Am J Gastroenterology 1996, 91(10):2174-8.
•
Hornbuckle K, JL Barnett. The diagnosis and work-up of the patient with gastroparesis. J Clin Gastroenterol
2000, Mar;30(2):117-24.
•
Karras PJ, Pfeifer MA. Diabetic gastrointestinal autonomic neuropathy. Curr Ther Endocrinol Metab 1997,
6:462-465.
•
Kendall BJ, McCallum RW. Gastroparesis and the current use of prokinetic drugs. Gastroenterol 1993,
1(2):107-114.
•
Koch KL. Gastroparesis: diagnosis and management. Article eight in the series. Practical Gastroenterol
1997, November. Pp 30-43.
67
References, Continued
•
McCallum RW. Clinical pharmacology forum: motility agents and the gastrointestinal tract. Am J Med Sci
1996, Jul;312(1):19-26
•
McCallum RW. Review of current status of prokinetic agents in gastroenterology. American Journal of
Gastroenterology 1985 80:1008-16.
•
Parkman HP et al. American Gastroenterological Association technical review on the diagnosis and treatment
of gastroparesis. Gastroenterology 2004 Nov;127(5):1592-1622.
•
Parkman HP et al. American Gastroenterological Association medical position statement: diagnosis and
treatment of gastroparesis. Gastroenterology 2004 Nov;127(5):1589-91
•
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, 11:2398-2404.
•
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):1456-62.
•
The Diabetes Institutes Foundation Website. Available at:
http://www.dif.org/DiabetesTopics/Gastroparesis.htm. Accessed Feb. 22, 2005.
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Enterra 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, extraabdominal 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 1-800-328-0810 and/or consult Medtronic’s website at www.medtronic.com.
USA Rx Only. Rev 0709
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