GASTROPARESIS

September 12, 2015SGNA

GASTROPARESIS

• Definition: a disorder in which patients exhibit signs and symptoms of delayed gastric emptying without an anatomic cause (obstructing ulcer, inflammatory stenosis, malignancy)

Causes of Gastroparesis

• Systemic disorder: diabetes mellitus, muscular dystrophy, amyloidosis, scleroderma

• Idiopathic: post-viral• Post-surgical: vagotomy, fundoplication

Symptoms of Gastroparesis

• Nausea• Vomiting• Abdominal pain• Early satiety• Heartburn• Dysphagia

CASE NM-1

• 30 YO female transferred to UH with nausea/vomiting

• “Flu” symptoms 4 mo prior• Hospitalized 2x in Ft Wayne:GB US, Abd CT,

HIDA, EGD all negative• Serology: mono, hep B, ANA: negative• Enteroclysis: “mucosal thickening in jejunum”

CASE NM- 2

• Exploratory lap: neg; feeding J tube, appy• Small intestinal Bx: neg• Transfer to UH• PMH: facial herpes zoster 2 yr PTA• Physical Exam: normal; normal liver and

spleen

CASE NM-3

• Lab: ALT 139, AST 36, GGTP 99• CMV (IgM) Pos 1:80 titer• GE scan: borderline slow gastric emptying• ID consult: transient viral illness

CASE NM-4

• Small intestinal manometry: abnormal MMC• EGG: abnormal: no increase in post-prandial

3 cpm activity• EGD: normal• Histology: acute/chronic inflammation• Antral Bx viral culture: CMV

Case NM-5

• Patient eating, discharged home; N/V return• Treatment with E-mycin, Reglan ineffective• EGD (6 mo after onset of Sx): NL; antral Bx

culture: CMV• 9 mo after onset of Sx: Rx with leuprolide

CASE NM- 6

• Good response to leuprolide: eating well, no N/V

• MONTH 13: leuprolide stopped• Month 17: hosp at IU with N/V, abd pain;

surgical J tube, decompression g tube• MONTH 30: Mayo Clinic: delayed gastric

emptying, delayed colon transit• Transient response to cisapride

CASE NM- 7

• Hosp IUMC with abdominal pain; colonoscopy shows ulcers: Bx pos CMV culture

• Rx with gancyclovir: colon ulcers heal, pain improves, vomiting and tube feeding continue

• Rx with domperidone: no response• Rx with leuprolide: no improvement

CASE NM-8

Gastric pacemaker implanted 8 yr after onset of Sx.Patient does well over next two years; J tube and G tube removed two years later.Patient require high current output from pacemaker and requires replacement every two years.

FACTORS REGULATING GI MOTILITY

• Intrinsic properties of visceral smooth muscle• Intrinsic and extrinsic nervous system• Gastrointestinal hormones

MOTOR FUNCTIONS OF THE STOMACH

• Accomodation• Mixing• Emptying• Sensation

ASSESSMENT OF GASTRIC EMPTYING

• Nuclear scan• Endoscopy• Ultrasound• “SMART” pill

PROBLEMS WITH NUCLEAR SCINTIGRAPHY

• Need standardized meal• Liquids empty faster than solids• Proteins and carbohydrates empty faster than

fats• Digestible solids empty faster than digestible

solids

ASSESSMENT OF GASTRIC ACCOMODATION

• SPECT scan• Barostat

ASSESSMENT OF GASTRIC SENSATION

• Satiety test

TREATMENT OF GASTROPARESIS

• Diet: low fat, low residue; supplements• Medications: avoid anticholinergics, narcotics• Promotility agents• Antiemetics• GJ tube feeding• TPN• Gastric electrical stimulation

PROMOTILITY AGENTS

• Reglan: FDA advisory: 3 months• E-mycin: suspension expensive• Domperidone: not FDA approved, insurance

coverage• Cisapride: drug interaction

ANTIEMETICS

• Phenergan: tablets, suspension, suppository, cream

• Zofran/Kytril: ODT, pill, patch• Marinol• Benadryl• Scopolamine • Ginger• Acupuncture

TUBE FEEDING

• Radiologic GJ tube• Endoscopic GJ tube• Surgical J tube• Venting gastrostomy optional• Temporary: gastric function may return after

several months of enteral nutrition

TPN

• Temporary measure• Enteral feeding effective in most patients• Infection• Thrombosis

GASTRIC ELECTRICAL STIMULATION

• How does it work?• Effective for nausea and vomiting• Does not “pace” stomach• May, or may not, accelerate gastric emptying• Lag phase: may take 6 months to work

GES SURGERY

• Laparoscopy• Risk of infection• Electrode migration• Warning: No MRI• FDA approved: not experimental• Insurance issues

RATIONALE FOR GASTRIC ELECTRICAL STIMULATION

• Cardiac pacing effective for some dysrhythmic disorders

• Stomach also has a “pacemaker” rhythm• Gastric “dysrhythmias” identified• Smooth muscle “pacemakers” identified in

small intestine, colon, ureter, bladder, uterus

Background

• ECA: electrical control activity; 3 cpm in humans, 5 cpm in dogs

• ERA: electrical response activity, ie gastric contractions

• GES entrains electrical activity in man and dogs

• Unclear whether GES can generate muscular contractions

Gastric Electrical Stimulation for Medically Refractory Gastroparesis

THOMAS ABELL, RICHARD McCALLUM, MICHAEL HOCKING, KENNETH KOCH, HASSE ABRAHAMSSON, ISABELLE LEBLANC, GREGER LINDBERG, JAN KONTUREK, THOMAS NOWAK, EAMMON M. M. QUIGLEY, GERVAIS TOUGAS, AND WARREN STARKEBAUM.

University of Mississippi, Jackson, Mississippi; University of Kansas, Kansas City, Kansas; University of Florida, Gainesville, Florida; Penn State University, Hershey, Pennsylvania; University of Goteborg, Sweden; Hospital Charles Nicolle, Rouen, France; Karolinska Institute, Stockholm, Sweden; Elbe Kliniken Stade, Stade, Germany; St.Vincent Hospital, Indianapolis, Indiana; National University of Ireland, Cork, Ireland; McMaster University, Hamilton, Ontario, Canada; and Medtronic, Inc., Minneapois, Minnesota.

GASTROENTEROLOGY 2003; 125: 421-428

EFFICACY OF GES

• Diabetic gastroparesis: 80-90%• Idiopathic: 70%• Postoperative: 60%

EFFECT OF GASTRIC STIMULATION ON CEREBRAL BLOOD FLOW IN

PATIENTS WITH GASTROPARESIS

Thomas V. Nowak1, Gary Hutchins2, Joel Hammond1, Yang Wang2,

Lyn Ring1 and Kativa Leal1

1Department of Medicine, St.Vincent Hospital, Indianapolis, Indiana, USA and

2 Department of Radiology, Indiana University Medical Center,Indianapolis, Indiana, USA.

PURPOSE

To determine whether GES produces changes in regional cerebral blood flow using positron emission tomography (PET).

CONCLUSIONS

• Gastric electrical stimulation of the stomach in gastroparetic patients produces significant alterations

in cerebral blood flow.

• Gastric electrical stimulation both increases and decreases blood flow to respective regions of the

brain.

• Central nervous system mechanisms during gastric electrical stimulation may be responsible for the

relief of nausea and vomiting in these patients.

GES: Issues Remain

• Mechanism: How does it work?• Which patients are best candidates for GES?• Optimal stimulus parameters• How to monitor treatment• Electrode placement: serosa, mucosa, fundus,

vagus nerve?• What about symptomatic patients with

normal or fast gastric emptying?

GES COLLABORATION

IU GASTROENTEROLOGY/HEPATOLOGY

PURDUE BIOMEDICAL/ELECTRICAL ENGINEERING

19 Aug 2013

76

[1] M.P. Ward et al. (In preparation - 2013). “A flexible closed-loop platform for rapid biofeedback control and personalization of electroceutical therapies.” [2] Richard M. Peek, Jr & Martin J. Blaser. (2002). “Helicobacter pylori and gastrointestinal tract adenocarcinomas.” Nature Reviews Cancer 2, pp. 28-37.

Experimental Setup

[2]

[1]

Diaphragm

Record VN Response

Stimulate Antrum

Record SM Response

[1]

Cutaneous Recordings of Vagal Afferents

78

Current and Future Directions

Finalize research objectives and submit proposals for funding

Biomarker discovery– Directly measure and characterize smooth muscle response– Multi-electrode recordings (ECoG electrodes)

fMRI studies– Purdue: Rodents– IUSM: GES patients

Investigate VNS as an alternative to GES

79