1. GASTROPARESIS Arnold Wald, M.D., AGA-F
University of Wisconsin School of Medicine & Public Health, Madison, WI

2. MAIN FUNCTIONS OF STOMACH
I PROXIMAL
Functions: Accommodation
Storage of ingested food
Regulation of intragastric
pressure
Tonic movement of chyme
Motor Pattern: Tonic activity
DISTAL
Functions: Grinding of food
Emptying to duodenum
Motor Pattern: Phasic activity

3. Motility of the Antral Pump Is Initiated by a Dominant Pacemaker in the Mid-corpus
Pacemaker potentials determine contractile parameters
Fundus
Contractile parameters
Max frequency (3/min)
Propagation velocity
Propagation direction
Pacemaker region
Pacemaker
potential
Motility of the Antral Pump Is Initiated by a Dominant Pacemaker in the Mid-Corpus
Gastric action potentials determine the duration and strength of the phasic contractions of the antral pump. They are initiated by a dominant pacemaker located in the corpus distal to the midregion. After they are started at the pacemaker site, the action potentials propagate rapidly around the gastric circumference and trigger a ring-like contraction. The action potentials and associated ring-like contraction then travel more slowly toward the gastroduodenal junction. Electrical syncytial properties of the gastric musculature account for the propagation of the action potentials from the pacemaker site to the gastroduodenal junction. The pacemaker region in humans generates action potentials and associated antral contractions at a frequency of 3 per minute. The gastric action potential is about 5 seconds long and has a rising (depolarization) phase, a plateau phase, and a falling (repolarization) phase.
Szurszewski JH. Electrophysiological basis of gastrointestinal motility. In: Johnson LR, Alpers DH, Christensen J, Jacobson ED, Walsh JH, eds. Physiology of the Gastrointestinal Tract. New York: Raven Press; 198:
Pylorus
Antrum
Corpus
The antral pump is formed by the mid and distal corpus, antrum, and pylorus B3
B87 3

4. % Meal remaining in stomach
Onset and Rate of Gastric Emptying Varies With the Composition of the Meal
Emptying phase
Lag phase
100
Solid meal 75
% Meal remaining in stomach 50
Semisolid meal
Onset and Rate of Gastric Emptying Varies With the Composition of the Meal
Liquids empty faster than solids when a mixed meal is in the stomach. If an experimental meal that consists of solid particles of various sizes that are suspended in water is instilled in the stomach, emptying of the particles lags behind emptying of the liquid. With digestible particles (eg, chunks of liver), the lag phase reflects the time that is required for the grinding action of the antral pump to reduce the particle size.
Meyer, JH. Motility of the stomach and gastroduodenal junction. In: Johnson LR, ed. Physiology of the Gastrointestinal Tract. 2nd ed. New York: Raven Press; 1987: 25
Liquid meal 20 40 60 80
100
Time after meal (min) B4 4

5. Gastric emptying – evolving concepts
Relationship with symptoms unclear
NOT nausea, vomiting or pain
Accelerating gastric emptying does not necessarily improve symptoms
Symptomatic improvement including weight gain is possible without improving gastric emptying
Gastroparesis is frequently overdiagnosed on the basis of outdated emptying tests

6. Causes of Gastroparesis
Idiopathic %
Diabetic %
Upper GI surgery 13%
Parkinson’s %
Collagen tissue disorder 5%
Intestinal pseudo-obstruction 4%
Miscellaneous (Incl eating disorders) %
Soykan et al, DDS 1998; 43:

7. Drugs that delay gastric emptying (Partial listing)
β Agonists
Anticholinergics
Tricyclic agents
Phenothiazines
Dopamine agonists
Opiates
Proton pump inhibitors
Miscellaneous
Dexfenfluramine Antihistamines
Lithium
Tetrahydrocannabinol
Tobacco

8. Workup for suspected gastroparesis
UGI Series: Excludes mechanical obstruction
Retention of barium w/o obstruction is diagnostic
Endoscopy: Bezoar without obstruction highly suggestive
Gastric Emptying: Solids more sensitive than liquids

9. Normal values for low fat, egg white GES
Lower normal limit Upper normal limit
Time for gastric retention* for gastric retention**
0.5 hr. 70%
1.0 hr. 30% 90%
2.0 hr %
4.0 hr %
* Lower value suggests rapid emptying
** Higher values suggest delayed emptying
Am J Gastroenterol 2008

10. Which of the following would you recommend:
2. A 30 y.o. woman with a one year history of type II diabetes mellitus presents with nausea and early satiety. Her blood sugars have been erratic and her last HBAIC was Endoscopy was normal and a gastric emptying test showed 20% retention of the meal at 4 hours (normal < 10%).
Which of the following would you recommend:
a) Metoclopramide
b) Rigorous control of blood sugars
c) Erythromycin
d) Botulinum toxin injection of the pylorus

11. Slow gastric emptying was frequent in women with type 2 diabetes with hyperglycemia and normalized after diabetic control
J Diabetes & Complications, 2013

12. A 23 y.o. woman developed a viral illness associated with fever, myalgias, nausea, vomiting and diarrhea. Although most of her symptoms resolved over 2 weeks, she continued to have nausea, occasional retentive vomiting, early satiety and a 10 lb. weight loss. Endoscopy showed a modest amount of retained food in the stomach and a gastric retention of a test meal consisting of egg whites, toast and jam at 4 hours was 35% (normal <10%).
Which of the following would you recommend first?
a) Metoclopramide
b) Botulinum toxin injection (pylorus)
c) Erythromycin
d) Gastric stimulator

13. Management of Gastroparesis
Dietary Modifications
Small frequent (6/day) meals
Reduced fat (<40 gm/day)
Soup, crackers, noodles, pasta,
potatoes, rice, cheese
Reduced fiber  helps avoid bezoar
Liquid caloric supplementation

14. Prokinetic Agents Motilides: erythromycin
ACh-esterase inhibitors: pyridostigmine
Motilides: erythromycin
Antidopamine agents: domperidone*
Antidopamine/serotonin agents:
metoclopramide
Serotonin agents: tegaserod*, prucalopride*
*Not available in USA

15. ERYTHROMYCIN Motilin agonist No antiemetic effect
Stimulates antral contractions
(IV >> PO)
Stimulates MMC
Dose: mg bid/tid (PO)
3 mg/kg q 8 hours (IV)

16. Metoclopramide Central/peripheral D2 antagonist and 5 HT agonist
Increases antral contractions
Decreases fundal relaxation
Improves antroduodenal coordination
Dose: mg qid (PO, IV, SQ, SL)

17. Metoclopramide * Boxed Warning for chronic use issued by FDA*
30% of patients experience side effects
10% have neurologic side effects
Parkinson-type syndrome
Tardive dyskinesia
Hyperprolactinemia
* Boxed Warning for chronic use issued by FDA*

18. Domperidone Peripheral D2 antagonist Increases antral contractions
Decreases fundal relaxation
Improves antroduodenal coordination
Dose: mg qid (PO)
Limited availability in USA

19. Efficacy of Domperidone in Diabetic Gastroparesis
□ Improved symptoms in 64%
□ Improved gastric emptying in 60%
□ Reduced hospital admission in 67%
□ 28 trials (19 double arm); 1016 patients
Sugumar A et al, CGH 2008

20. Effects of Botulinum Toxin on GE and GI Symptoms
Within Group
Between Group P
Botox P
Placebo
Improved %
37.5
56.3
0.29
GCSI score
0.01
0.42
GVAS score
0.02
0.88
% Gastric retention 2 hr
0.08
0.52
% Gastric retention 4 hr
0.62
0.27
Friedenberg FK, et al. Am J Gastro 2008

21. 3. A 28 y.o. man with IDDM is referred for chronic and recurrent nausea and vomiting. He reports 3-4 episodes yearly for the past 5 years with frequent ED visits or hospitalizations lasting 3-4 days. Between episodes, he feels well and has lost no weight. During these episodes, he finds great relief when taking hot showers.
The most appropriate intervention for this patient is:
a) Domperidone 20 mg AC meals
b) Nortriptyline in doses up to 100mg hs
c) Discontinue smoking marijuana
d) Strict control of blood sugars; metoclopramide mg SQ during episodes

22. Cyclic Vomiting Syndrome
Recurrent and stereotypical episodes of severe nausea and vomiting separated by symptom free intervals
- Gastric emptying rapid or normal
- Maintenance of weight

23. Cannabinoid Hyperemesis
- Cyclic vomiting syndrome
- Compulsive hot water bathing
- Poor response to TCAs

24. Cyclic Vomiting in Adults (Non-Cannabinoid)
Association with migraine headaches
Psychological disorders (anxiety/depression)
Absence of compulsive hot water bathing
Often responds to TCAs

25. References
1. Hasler WL. Gastroparesis: pathogenesis, diagnosis and management. Nat Rev Gastroenterol Hepatol 2011;8:
2. Choung RS et al. Cyclic vomiting syndrome and functional vomiting in adults. Neurogastroenterol Motil 2011;24:20-26