Evaluation and Management of Evaluation and Management of Patients with Gastroparesis

John I Allen, MD, MBA, AGAF

Minnesota Gastroenterology PAgy

University of Minnesota School of Medicine

Vice President – American Gastroenterological AssociationVice President American Gastroenterological Association

Major Take Home Points

Definition and Facts About Gastric Emptyingp y g

Practical Evaluation for Gastroparesis

Initial Stepped Approach to TreatmentInitial Stepped Approach to Treatment

How to Manage the Patients that are not easy

When to consider an enteral feeding tube or Gastric Electrical Stimulation

Digestive Mechanism - Simplified

UESFood bolus Food bolus transported along esophagus

(7-10”, 25 cm long)

Gravity &Peristalsis

LES

LES relaxes to allow food to pass into the stomach

Impulses generate gastric peristalsisLES

PacemakerImpulse

Impulses generate gastric peristalsis

HClHClFood is mixed and ground, chemically broken-down, ingested microbes killed

Pylorus Closed

Sphincter of Oddi

Bile Digestive

Pylorus controls the emptying of the food into the duodenum

gJuice

Via sphincter of Oddi, bile emulsifies fats, pancreas secretes digestive juice and transports wastes into the rectum

Anal SphincterClosed

Gastric Motility

In its resting state, the stomach is small and contains gabout 50 ml of fluid

Swallowing causes the fundus to relax (receptive l ti ) t i b l f f d f th relaxation) to receive a bolus of food from the

esophagus

Relaxation is coordinated by vagal fibers and is Relaxation is coordinated by vagal fibers and is facilitated by gastrin and cholecystokinin (two polypeptide hormones secreted by the GI mucosa)

Gastric Motility

Mixing occurs as food is propelled to the g p pantrum

As food approaches the pylorus, peristaltic pp py , pwaves force contents back toward the body (retropulsion)

Mixes food with digestive juices and breaks down large food Mixes food with digestive juices and breaks down large food particlesPylorus = 1.5 cm long/always open about 2.0 mm

Opens wider during antral contractionNormally no regurgitation from duodenum to antrum

Gastric Emptying

Rate depends on:200 Kcal/hourVolume

Osmotic pressureChemical composition of gastric contents

200 Kcal/hour

p g

Larger volumes of food increase gastric pressure peristalsis and rate of emptyingpressure, peristalsis, and rate of emptying

Solids, fats, and non-isotonic solutions delay t i t igastric emptying

Certain hormones inhibit gastric motility gthereby delaying emptying

Gastric Emptying Ratesp y g

Camilleri M. NEJM 2007; 356:820

Patient # 1: “I throw up” 44 year old man with Type II Diabetes is referred from the ED with recurrent vomiting. 18 ED visits in the last 6 months for pain and sedation medications fluids and months for pain and sedation medications, fluids and anti-emetics. He complains of abdominal pain, constant nausea and vomiting at least 8 times weekly. His HgbA1c is 9.4. Endoscopy, RUQ US, HIDA Scan and CT (with is 9.4. Endoscopy, RUQ US, HIDA Scan and CT (with Enterography) all were normal. A solid phase Gastric Emptying Study was abnormal.

Consider the key points from his history, physical exam, initial laboratory values and imaging.

Camilleri et al Epidemiology Mechanisms and Management of Diabetic Camilleri et al. Epidemiology, Mechanisms and Management of Diabetic Gastroparesis. Clin Gastro Hep 2011; 9:5-12.

Diabetic Gastroparesis Delayed gastric emptying in absence of mechanical obstruction.

P t di l f ll iti ( ft f ld f d) d Post-prandial fullness, nausea, vomiting (often of old food) and bloating.

Diabetes = 1/3 of all GP/

5-12% of patients with diabetes have symptoms of GP.

Prevalence of definite GP in the population (2007) was 24/100 000Prevalence of definite GP in the population (2007) was 24/100,000

Diabetics with GP – worse with poor glycemic control but persists4.8% Type I4.8% Type I1% Type IIO.1% of non-diabetics

Additional Causes

Post-viral

Anorexia nervosa

Meds (narcotics, anti-cholinergics)Bentyl, Antivert, Phenergan, Cogentin, Atrovent, Ditropan

Amyloid and scleroderma

ddiAddisons

Migraines

Hypothyroidism

Evaluation of Symptoms

History and physical examinationMedications and past treatments

E d d SBFT (CT MR E t h )Endoscopy and SBFT (CT or MR Enterography)

Lactose, Fructose, Glucose Breath Tests

Ultrasound and possible Nuclear GB Scan

Solid phase Gastric Emptying Study or Capsule Motility

Evaluation for Central causes (Neurological, Tumor)

Scintiscans of Residual Gastric Contents

Camilleri M. N Engl J Med 2007;356:820-829

Blood Sugar SignalsLow Blood Sugar High Blood Sugar = Insulin

CravingsDepression

Increased Gastroparesis ActivityInflammation

g g

DepressionFatigue

InsomniaLack of Focus

Irritable

Fat StorageWeight gain

High CholesterolHigh Triglycerides

High Blood Pressure

Blood Sugar Levels

200Balanced Blood Sugar

80

100

120

140

160

180

Suga

r Lev

el

Decrease in Gastroparesis ActivityIncreased Energy

Weight LossEven Moods

0

20

40

60

80

1/2 1.0 1 1/2 2.0 2 1/2 3.0 3 1/2 4.0 4 1/2

Bloo

d Eliminate CravingsLower Cholesterol

Sense of Well-Being

Hours Since Last Meal/Snack

Balanced Blood Sugar Fluctuations Erratic Blood Sugar Fluctuations

© 2/2011 Minnesota Gastroenterology, PA. (612) 871-1145

Management ProgressionManagement ProgressionLeast invasive/risky

Lif t lLifestyle

Pharmacologya aco ogy

Tube feeding

Gastric Pacing

SMost invasive/risky

Surgery

Total parental nutritionTotal parental nutrition

Lifestyle Changes

Mild (Gastric Retention 10-15% at 4 hours)Low fatSmall mealsTobacco cessation

Moderate (16-35%)Periodic homogenized food

Severe (>35%)Homogenized foodOften with J tube (10% weight loss in 6 months)( g )

Medical Treatments

Reverse underlying conditionsOptimize glucose and electrolyte levels

Medication ReviewMedication ReviewAnti-hypertensive meds (calcium channel blockers)Anti-cholinergics (anti-depressants)Exenatide and pramlintide (hyperglycemia meds)Exenatide and pramlintide (hyperglycemia meds)

Anti-emeticsTricyclic Anti-depressants

86% at least moderate improvementAmitriptyline or nortriptylineAmitriptyline or nortriptyline

10-100 mg dailyStart with 10-20 mg at bedtime and work up in 10 mg increments over several weeksSedative side effects

BenzodiazepinesLorazepam (Ativan) – anxiety – 1-2 mg PO q day

Cannabinol (Marinol) 2 5 5 mg BIDCannabinol (Marinol) 2.5 – 5 mg BIDApepritant (Emend) 80 mg dailyAcupuncture (P6) or Relief BandAcupuncture (P6) or Relief Band

Prokinetics

Promote antral contractility

Antiemetic qualities

Metoclopramide (acetylcholine release and inhibition of Metoclopramide (acetylcholine release and inhibition of dopamine receptor)

Proximal gut onlySide effects 50% - Medical Legal Riskg

Parkinsons, somnolence, tardive dyskinesia, depression, breast engorgementDetailed documentation needed10 mg 30 minutes prior to meals (20 mg QID)

ProkineticsDomperidone (Motilium) – peripheral acting dopamine-2 antagonist

Does not cross BB barrieroes o c oss ba e10 mg before meals and q HS (max 30 mg QID)Need at least 3 months of therapyBreast engorgement, irregular mensesCanada New Zealand TexasCanada, New Zealand, Texas

www.fda.gov/cder/news/domperidone.htm

Tegaserod – withdrawn March 2007Macrolide antibiotics

Erythromycin 2-3 mg/kg IV q 6 or 125-250 mg TID (suspension)

Abdominal Pain

89% of patients with gastroparesisp g p

Acetaminophen and NSAIDʼs

IV ketorolac can be used to interrupt gastric dysrythmias IV ketorolac can be used to interrupt gastric dysrythmias in DM hospitalized for gastroparesis

15-30 mg IV q 6 hours

Tramadol 50-100 mg PO q 6

Gabapentin 100-1200 mg TID (Neurontin)

Abdominal Pain

Tricyclic Anti-depressantsSSRIʼs

Panic attacks – Paroxetine (Paxil) Remeron – increase appetite and sedationEffexor and Cymbalta chronic painEffexor and Cymbalta – chronic pain

Short acting narcotics – oxycodone, ms, dilaudidLong acting narcotics – oxycontin, MScontin or Long acting narcotics oxycontin, MScontin or transdermal fentanyl (or Actique lozenges – 400 micrograms of fentanyl)Alvimopan(Entereg) 6 mg/day –blocks intestinal effects of narcotics (recently withdrawn)effects of narcotics (recently withdrawn)

Jejunal Feeding Tube Gastrostomy or GJ Tubey

Enterra Therapy: U. S. Indication

“Enterra Therapy is indicated for the 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.”g g

Gastric Electrical StimulationGastric Electrical Stimulation

Lead FixationLead Fixation

Stimulator PocketStimulator Pocket

Conclusion: What are we missing and How Can we Help?How Can we Help?