Review

Digestion 2008;78:173179 Published online: December 18, 2008

DOI: 10.1159/000185690

Treatment of Gastroparesis: An Update

Vivek Gumaste Joel Baum
Department of Medicine, Mount Sinai Services at Elmhurst, Elmhurst General Hospital, Elmhurst, N.Y., and
Mount Sinai School of Medicine of the City University of New York, New York, N.Y., USA

Key Words ing scintigraphy, is present in 2555% of patients with

Gastroparesis Diabetes type 1 diabetes and in 30% of those with type 2 diabetes
[25]. Considering the widespread prevalence of diabe-
tes, this would constitute a significant proportion of the
Abstract population.
Gastroparesis is a chronic disorder of gastric motility that is
characterized by delayed emptying of either solids or liquids
from the stomach in the absence of any mechanical obstruc- Etiology
tion. Nausea, vomiting, early satiety and bloating are some
of the manifestations of gastroparesis. Idiopathic, diabetes The etiology of gastroparesis is diverse with the idio-
mellitus and postsurgical states account for the majority of pathic variety constituting the largest group in one study
cases. Gastroparesis is a difficult condition to treat. Prokinet- [6]. Diabetes accounted for 29% of patients in that same
ic drugs like metoclopramide and erythromycin form the report with postsurgical causes making up 13%. These 3
mainstay of therapy but are less than ideal. Some patients causes (idiopathic, diabetes and postsurgical) account for
may benefit from endoscopic botolinium toxin injection. a majority of all cases. Other causes of gastroparesis in-
Gastric electrical stimulation, though promising, is not ready clude neurological conditions like Parkinsonism, colla-
for prime time yet. Copyright 2008 S. Karger AG, Basel gen vascular diseases, Chagas disease, hypothyroidism,
hyperparathyroidism and hypoparathyroidism.

Gastroparesis is a chronic disorder of gastric motility Clinical Manifestations and Diagnosis

that is characterized by delayed emptying of either solids
or liquids from the stomach in the absence of any me- Present studies indicate that the majority of those with
chanical obstruction. Gastroparesis assumes clinical im- delayed gastric emptying are women and the mean age of
portance because it can contribute to upper gastrointes- onset is 34 years [6].
tinal symptoms like nausea, vomiting and early satiety. Gastroparesis manifests itself through a combination
The precise incidence of gastroparesis is not known, of symptoms. Most symptoms are nonspecific and over-
but it is estimated to affect about 4% of the population [1]. lap with common gastrointestinal disorders like peptic
Gastroparesis, as documented by delayed gastric empty- ulcer disease and nonulcer dyspepsia. Nausea/vomiting,

2008 S. Karger AG, Basel Assoc. Prof. Vivek Gumaste, MD

00122823/08/07840173$24.50/0 Mount Sinai School of Medicine
Fax +41 61 306 12 34 Division of GI, Elmhurst General Hospital
E-Mail [email protected] Accessible online at: 79-01 Broadway, New York, NY 11373 (USA)
www.karger.com www.karger.com/dig Tel. +1 718 334 2288, Fax +1 718 334 1738, E-Mail [email protected]
Table 1. Proposed classification of gastroparesis severity Table 2. Medications associated with impaired gastric emptying

Grade 1: Mild gastroparesis Narcotic pain medications

Symptoms relatively easily controlled Tricyclic antidepressants
Able to maintain weight and nutrition on a regular diet or minor Calcium channel-blocking medications
dietary modifications Clonidine
Dopamine agonists
Grade 2: Compensated gastroparesis
Lithium
Moderate symptoms with partial control with pharmacological
Nicotine
agents
Progesterone containing medications
Able to maintain nutrition with dietary and lifestyle adjustments
Muscarinic cholinergic receptor antagonists
Rare hospital admissions
Grade 3: Gastroparesis with gastric failure
Refractory symptoms despite medical therapy
Inability to maintain nutrition via oral route
Frequent emergency room visits or hospitalizations

Reproduced from Abel et al. [9]. intermittent symptoms that are controlled with diet
modification and avoidance of exacerbating agents.
Grade 2 patients have moderately severe symptoms but
no weight loss and require prokinetic drugs plus anti-
emetic agents for control. In Grade 3, patients are refrac-
postprandial fullness/early satiety and bloating are the tory to medication, unable to maintain oral nutrition
commonest manifestations. Nausea is the most consis- and require frequent emergency room visits. These pa-
tent symptom found in over 90% of patients [6, 7]. Bloat- tients require intravenous fluids, medications, enteral
ing and early satiety are present to a lesser degree, being or parenteral nutrition and endoscopic or surgical ther-
found in 75% and 60%, respectively, in one study [6]. apy.
Abdominal pain may be present in 4689% of patients
but is unlikely to be the predominant symptom [6, 7].
As the symptoms are nonspecific with a significant Treatment
degree of overlap with other gastric disorders, the initial
work-up should include an upper endoscopy, even if gas- A wide array of therapeutic interventions is available
troparesis is strongly suspected. This is necessary to rule to treat gastroparesis. Diet modification, pharmacologi-
out any mechanical obstruction and other common dis- cal agents, endoscopic techniques, surgery and psycho-
orders like peptic ulcer diseases and nonulcer dyspep- logical counseling are some of the modalities em-
sia. ployed.
When an upper endoscopy does not reveal any organ-
ic obstruction and the endoscopic findings do not ade- General and Dietary Measures
quately explain the patients symptoms, a definitive test While there are no controlled trials testing the effi-
to diagnose gastroparesis such as gastric scintigraphy cacy of diet modification in the therapy of gastroparesis,
must be done. some dietary recommendations may prove helpful in pa-
tients with milder forms of the disease. Multiple small
meals a day as opposed to 2 or 3 large meals facilitate gas-
Assessment of Severity tric emptying. Generous intake of fluids during a meal
may aid gastric emptying, as liquids empty more rapidly
Assessment of severity is important for appropriate than solids. An overall reduction in the solid food content
management. One method is the Gastroparesis Cardinal is also advised. A diet low in fats decreases the inhibitory
Symptom Index (GCSI), which is a sum, total of 3 sub- effect of lipids on gastric emptying. Patients should be
scales (ranging from 13) for the 3 main symptom com- told to avoid a high fiber diet to prevent phytobezoar for-
plexes: postprandial fullness/early satiety, nausea/vomit- mation.
ing and bloating [8]. Proper mastication and postprandial walking are ad-
Another simple gradation of severity is outlined in ditional factors that may facilitate the gastric emptying
table 1 [9]. Grade 1 usually includes patients with mild process.

174 Digestion 2008;78:173179 Gumaste/Baum

Table 3. Prokinetic agents Table 4. Efficacy of metoclopramide in gastroparesis

Agent Mechanism Dosage Study n Design Symptom GE im-

reduction provement
Metaclopramide dopamine D2 receptor 520 mg q.i.d.
antagonist Perkel et al. [13] 28 RDBP yes not stated1
Domperidine dopamine D2 receptor 1030 mg q.i.d. Snape et al. [12] 10 RDBP yes yes
antagonist McCallum et al. [11] 40 DBP yes yes
Erythromycin motilin receptor agonist 50250 mg q.i.d. Ricci et al. [14] 13 RDBP yes yes
Bethanechol muscarinic receptor agonist 25 mg q.i.d.
Pyridostigmine acetylcholinestrase inhibitor 3060 mg t.i.d. Metoclopramide vs. cisapride
Tegaserod 5-HT4 receptor agonist withdrawn in US De Caestecker et al. [15] 19 DBP No no
Cisapride 5-HT4 receptor agonist withdrawn in US Metoclopramide (M) vs. erythromycin (E)
Loxiglumide CCK receptor antagonist under study Erbas et al. [16] 13 OL yes (E>M) yes
Metoclopramide (M) vs. domperidone (D)
Patterson et al. [18] 45 RDB yes not studied
Dumitrascu et al. [17] 10 DB yes (D>M) yes (D>M)

GE = Gastric emptying; RDBP = randomized double-blind

Medicines that decrease gastric motility should be dis- placebo controlled; DBP = double-blind placebo controlled; OL =
continued if possible (table 2). Identification and correc- open label; RDB = randomized double blind; DB = double blind.
tion of the underlying cause of gastroparesis may be help- 1 Used barium studies to measure gastric emptying.

ful in some cases. In diabetics, aggressive control of blood

sugar is advocated as it is thought to facilitate the action
of other therapeutic measures.

Prokinetic Agents study [16]. Other studies [17, 18] have shown that meto-
There are 3 broad classes of prokinetic agents used in clopramide may be equally effective or marginally infe-
the treatment of gastroparesis: dopamine receptor antag- rior to domperidone in efficacy.
onists, motilin receptor agonists and 5-HT4 receptor ago- Patients may develop tolerance over time and uncom-
nists (table 3). fortable side effects may limit its use in up to 30% of pa-
tients. Irreversible tardive dyskinesia is a serious side ef-
Dopamine Receptor Antagonists fect that occurs in 110% of patients treated for more than
Metaclopramide. Metaclopramide is a 5-HT4 agonist, 3 months [19]. Therefore, it is not advisable to maintain
a dopamine D2 receptor antagonist and a direct stimulant patients on metaclopramide for a prolonged period.
of smooth muscle, all of which contributes to its proki- When initiating therapy, the side effects should be dis-
netic effect [1]. In addition to accelerating gastric motil- cussed and documented in the patient record.
ity, metaclopramide has an independent antiemetic ef- Domperidone. Domperidone is a peripheral dopamine
fect. Metaclopramide can be administered intravenously, D2 receptor antagonist with prokinetic properties and a
subcutaneously or through the oral route. A liquid prep- potent antiemetic effect. As it does not cross the blood-
aration is also available. brain barrier, its central nervous system side effects are
Although there are several studies [1018] that have minimal.
attempted to document the efficacy of metoclopramide In clinical trials, the efficacy of domperidone matches
in gastroparesis, most of them suffer from significant de- that of metaclopramide and cisapride [18]. However, its
sign flaws or insufficient numbers. Some of the more ac- effect on solid-phase gastric emptying is lost by 6 weeks
ceptable trials are listed in table 4. The overall conclusion [20]. The drug is not approved in the United States by the
that can be drawn from these trials is that a minority of FDA but can be made available through special applica-
patients may experience symptom benefit from metoclo- tion for patients with refractory gastroparesis.
pramide therapy. However, there appears to be poor cor-
relation between the improvement in gastric emptying Motilin Receptor Agonists
and reduction of symptoms. Erythromycin. Erythromycin exerts its prokinetic ef-
When compared to erythromycin, metoclopramide fect by stimulating the motilin receptors on smooth mus-
proved to be inferior in terms of symptom relief in one cles and neurons in the gastroduodenal area [21]. How-

Treatment of Gastroparesis Digestion 2008;78:173179 175

ever, unlike metaclopramide, erythromycin has no inde- Table 5. Efficacy of erythromycin in gastroparesis
pendent antiemetic effect.
Study n Design Route Symptom GE improve-
Most published trials [2226] reporting on the efficacy reduction ment
of erythromycin in gastroparesis have been open labeled,
had inadequate numbers or lacked strict definitions [22]. Richards et al. [25] 10 OL PO, IV yes yes
A few representative studies are outlined in table 5. The Ramirez et al. [24] 16 OL PO, IV yes yes
conclusion gleaned from these reports is that though Fiorucci et al. [23] 12 OL IV not stated yes
Samsom et al. [26] 12 DBC PO unclear not done
erythromycin improves gastric emptying, it benefits only
a minority of patients with regard to symptom ameliora- GE = Gastric emptying; OL = open label; PO = per os; IV =
tion. intravenous; DBC = double-blind controlled.
Erythromycin can be administered intravenously in
hospitalized patients or provided in liquid form or oral
tablets to outpatients. Its most potent effect is seen when
injected intravenously [27]. The oral route (125250 mg,
34 times daily) is less efficacious. Tolerance is known to Table 6. Overview of studies with botulinium toxin injection in
occur with chronic use. An increased incidence of sudden gastroparesis
cardiac death in patients using erythromycin has been
Study n Dose Follow-up Symp- GE
reported [28]. tom re- improve-
Other Motilin Receptor Agonists. Mitemcinal, a new duction ment
motilin agonist, which can be administered orally, has
shown promise in initial trials [29]. Ghrelin, an endoge- Open
Ezzedine et al. [33] 6 100 IU 6 weeks 55% 52%
nous neurohumoral mediator, is currently under study Miller et al. [34] 10 100 IU 4 weeks 38% 48%
[30]. Arts et al. [36] 20 100 IU 1 month 29% 35%
Lacy et al. [35] 8 200 IU 12 weeks 55% 33%
5-HT4 Receptor Agonists Bromer et al. [32] 63 200 IU 2 months 43% NS
Tegaserod and Cisapride are 5-HT4 receptor agonists, Randomized placebo-controlled trials
which have been used to treat gastroparesis in the past. Arts et al. [38] 23 100 IU 1 month none none
Both agents were withdrawn from use in the United States Friedenberg et al. [39] 16 200 IU 1 month none im-
proved
owing to serious cardiovascular complications [1].
GE = Gastric emptying; NS = not significant.
Symptomatic Therapy
Antiemetic drugs have been used successfully in clin-
ical practice to treat the symptoms of gastroparesis al-
though hard evidence for this rationale in the form of
scientific studies is minimal. The most commonly used Table 7. Trials with gastric electrical stimulation
antiemetic drugs are the phenothiazines (for example
prochlorperazine and thiethylperazine) and they can be Study Design n Duration Symptom
used in conjunction with prokinetic agents [9]. months improvement
Low-dose tricyclic antidepressants may provide relief
GEMS [42] open 33 12 yes
of symptoms in patients with gastroparesis [31]. WAVESS [43] DBS 33 2 yes
Pain may be a prominent symptom in some patients. open 33 12 yes
Nonsteroidal agents, selective serotonin reuptake inhibi- Forster et al. [40] open 25 12 improved at 3 months
tors and opiates have been used with varying degrees of sustained at 12 months
Forster et al. [44] open 55 12 improved at 6 months
success [9].
not sustained at
12 months
Endoscopic Treatment Lin et al. [45] open 55 36 improved at 1 year
In some patients with gastroparesis, pylorospasm may sustained for 3 year
contribute to a delay in gastric emptying. Endoscopic Anand et al. [46] open 214 48 sustained for 4 year
therapy involves the injection of botulinium toxin (100
DBS = Double-blind sham.
200 units in a circumferential pattern; 4 injections around

176 Digestion 2008;78:173179 Gumaste/Baum

Table 8. Consensus recommendations for the treatment of gastroparesis

Psychological Glycemic control Nutritional care Prokinetic medications Antiemetic therapy Pain control
measures

Empathy and Twice daily long- Small, frequent meals, Metoclopramide or Phenothiazine or dopamine Acetaminophen or
education acting insulin plus low in fat and fiber erythromycin PRN receptor antagonist PRN nonsteroidal agents
Patient support periprandial short- Primarily liquid diet Metoclopramide or Muscarinic receptor Tramadol or
groups acting insulin Liquid nutrient erythromycin scheduled antagonist or 5-HT3 propoxyphene
Behavioral or Insulin pump supplements dosing antagonist Tricyclic agents
relaxation therapy Pancreas transplant Enteral feedings Domperidone or Tricyclic agents Newer antidepressants
Hypnosis Central or peripheral tegaserod Tetrahydrocannabinol, TCAs, SNRIs
parenteral nutrition Pyloric botulinum toxin lorazepam or alternative Fentanyl patch or
short term therapies methadone
Gastric electrical Referral for pain specialist
stimulation Nerve block

A stepped care approach in a top-down vertical manner is recommended which is dependent on the severity of gastroparesis. Treatment from differ-
ent categories (columns) is often used in combination. TCA = Tricyclic antidepressant agent; SNRI = selective norepinephrine reuptake inhibitor. Re-
produced from Abel et al. [9].

the pylorus) into the pyloric area, which is thought to de- Initial experience with gastric stimulators was ob-
crease pylorospasm and accelerate gastric emptying. tained through 2 multicenter trials, the Gastric Electrical
Several open-labeled studies [3237] indicated a good Mechanical Stimulation Study (GEMS) [42] and the
symptomatic response (table 6) with symptom scores Worldwide Anti-Vomiting Electrical Stimulation Study
falling by 2955%. Gastric emptying rates also registered (WAVESS) [43]. GEMS was a multicenter open-labeled
a marked improvement (3352%) and correlated well trial that documented improvement in nausea and vom-
with symptom reduction. The effect of botulinium toxin iting in gastroparetic patients. WAVESS was a controlled
lasted up to 5 months in one study [32]. double-blind sham stimulation trial that reaffirmed the
However, the results from 2 randomized, placebo- efficacy of gastric stimulation and paved the way for FDA
controlled trials [38, 39] have not been encouraging. Arts approval of the Enterra system.
et al. [38] failed to demonstrate any beneficial effect on All trials [40, 4446] have produced encouraging re-
either gastric emptying or symptoms over placebo. In the sults with patients experiencing 7580% reduction in
study by Friedenberg et al. [39], gastric emptying rates symptoms (table 7). While some initial studies showed
improved, but provided no symptom benefit. More stud- conflicting results with regard to sustenance of improve-
ies are required before reaching a final verdict on botu- ment [40, 44], two subsequent studies have indicated
linium toxin injection therapy. long-term benefits lasting 3 and 4 years, respectively [45,
Dilation of the pylorus may produce the same benefit 46]. Cutts et al. [47] were able to demonstrate that gastric
as botulinium injection [1]. stimulation therapy is superior to intensive medical treat-
ment.
Gastric Electrical Stimulation About 10% of patients, however, develop complica-
Using exogenous electrical current to stimulate the tions like infection, which invariably warrants removal of
stomach in patients with gastroparesis is a logical and at- the device. Other adverse events noted include: lead dis-
tractive concept. Initial methods involved external leads, lodgement, wire breakage, penetration of the stomach
which were too large for implantation and unwieldy [40]. and intestinal obstruction, all of which require surgical
Recently, the FDA has given limited approval on human- intervention [41].
itarian grounds for a gastric electrical stimulator with a New methods that involve electrodes that can be
pulse generator that can be implanted into the abdominal placed orally by endoscopy or through a percutaneous
wall (Enterra gastric electrical stimulation system). The endoscopic gastrostomy [48] or by percutaneous tech-
pulse generator delivers low-energy, high-frequency niques [49] are also being explored.
stimuli and has a battery life of 68 years [41]. This meth- Gastric electric stimulation is not ready for prime time
od is, at present, limited to a few centers. yet. Available devices need to undergo further refinement

Treatment of Gastroparesis Digestion 2008;78:173179 177

and easier electrode implantation techniques that obviate Total parenteral nutrition maybe necessary in patients
the need for surgery are required. Long-term controlled who have concomitant intestinal motility.
studies involving larger numbers will be necessary for
gastric electrical stimulation to be accepted as standard Psychological Support
therapy [50, 51]. Anxiety, depression and somatization are increasingly
found in patients with severe gastroparesis and appropri-
Surgery ate psychological support is necessary to improve the
Extreme cases may require surgical intervention, and overall well-being of the patient. Psychotherapeutic mea-
operations like partial gastrectomy and pyloroplasty have sures like relaxation techniques have been useful. Some
been performed to treat resistant gastroparesis. The re- patients benefit from hypnosis and biofeedback [9].
sults are unproven so far.
Rarely, a venting gastrostomy may be placed to release
the discomfort from gas and liquids [1]. Conclusion

Enteral and Parenteral Nutrition Most therapeutic measures available to treat gastropa-
Some patients with severe refractory gastroparesis may resis are less than ideal and patients may require a com-
need enteral or parenteral modes of nutritional support. bination of measures depending on the severity of their
Enteral nutrition is usually indicated in patients with sig- condition. Table 8 summarizes the overall approach to
nificant malnutrition (110% weight loss over 6 months), the treatment of gastroparesis.
evidence of mineral deficiencies and electrolyte imbalance
and in those who require frequent hospitalizations [1].

References

1 Hasler WL: Gastroparesis: Symptoms, Eval- 9 Abel TL, Bernstein RK, Cutts T, et al: Treat- 16 Erbas T, Varoglu E, Erbas B, Tastekin G,
uation, and Treatment. Gastroenterol Clin N ment of gastroparesis: a multidisciplinary Akalin S: Comparison of metoclopramide
Am 2007;36:619647. clinical review. Neurogastroenterol Motil and erythromycin in the treatment of dia-
2 Kong M-F, Horowitz M, Jones KL, et al: Nat- 2006;18:263283. betic gastroparesis. Diabetes Care 1993; 16:
ural history of diabetic gastroparesis. Diabe- 10 Parkman HP, Hasler WL, Fisher RS: Ameri- 15111514.
tes Care 1998;22:503507. can Gastroenterological Association techni- 17 Dumitrascu DL, Weinbeck M: Domperi-
3 Nowak TV, Johnson CP, Kalbfleisch JH, et al: cal review on the diagnosis and treatment of done versus metoclopramide in the treat-
Highly variable gastric emptying in patients gastroparesis. Gastroenterology 2004, 127: ment of diabetic gastroparesis. Am J Gastro-
with insulin dependent diabetes mellitus. 15921622. enterol 2000; 95: 316317.
Gut 1995;37:2329. 11 McCallum RW, Ricci DA, Rakatansky H, et 18 Patterson D, Abell T, Rothstein R, Koch K,
4 Moldovan C, Dumitrascu DL, Demian L, et al: A multicenter placebo-controlled clinical Barnett J: A double-blind multi-center com-
al: Gastroparesis in diabetes mellitus: an Ul- trial of oral metoclopramide in diabetic gas- parison of domperidone and metaclo-
trasonographic study. Rom J Gastroenterol troparesis. Diabetes Care 1983;6:463467. pramide in the treatment of diabetic patients
2005;14:1922. 12 Snape WJ Jr, Battle WM, Schwartz SS, Braun- with symptoms of gastroparesis. Am J Gas-
5 Horowitz M, Su YC, Rayner CK, et al: Gas- stein SN, Goldstein HA, Alavi A: Metoclo- troenterol 1999;94:12301234.
troparesis: prevalence, clinical significance pramide to treat gastroparesis due to diabe- 19 Ganzini L, Casey DE, Hoffman WL, et al:
and treatment. Can J Gastroenterol 2001; 15: tes mellitus: a double-blind, controlled trial. The prevalence of metaclopramide- induced
805813. Ann Intern Med 1982;96:444446. tardive dyskinesia and acute extrapyramidal
6 Soykan I, Sivri B, Saosiek I, et al: Demogra- 13 Perkel MS, Moore C, Hersh T, Davidson ED: movement disorders. Arch Intern Med 1993;
phy, clinical characteristics, psychological Metoclopramide therapy in patients with de- 153:14691475.
and abuse profiles, treatment, and long term layed gastric emptying: a randomized, dou- 20 Horowitz M, Harding PE, Chatterton BE,
follow-up of patients with gastroparesis. Dig ble-blind study. Dig Dis Sci 1979; 24: 662 Collins PJ, Sherman DJC: Acute and chronic
Dis Sci 1998;43:23982404. 666. effects of domperidone on gastric emptying
7 Hoogerwerf WA, Pasricha PJ, Kalloo AN, et 14 Ricci DA, Saltzman MB, Meyer C, Callachan in diabetic autonomic neuropathy. Dig Dis
al: Pain: the overlooked symptom in gastro- C, McCallum RW: Effect of metoclopramide Sci 1985;30:19.
paresis. Am J Gastroenterol 1999; 94: 1029 in diabetic gastroparesis. J Clin Gastroenter- 21 Peters TL: Erythromycin and other macro-
1033. ol 1985;7:2532. lides as prokinetic agents. Gastroenterology
8 Revicki DA, Rentz AM, Dubois D, et al: De- 15 de Caestecker JS, Ewing DJ, Tothill P, Clarke 1993;105:18861899.
velopment and validation of a patient-as- BF, Heading RC: Evaluation of oral cisapride 22 Maganti K, Onyemere K, Jones MP: Oral
sessed gastroparesis symptom severity mea- and metoclopramide in diabetic autonomic erythromycin and symptomatic relief of gas-
sure: the Gastroparesis Cardinal Symptom neuropathy: an eight-week double-blind troparesis: a systematic review. Am J Gastro-
Index. Aliment Pharmacol Ther 2003; 18: crossover study. Aliment Pharmacol Ther enterol 2003;98:259263.
141150. 1989;3:6981.

178 Digestion 2008;78:173179 Gumaste/Baum

23 Fiorucci S, Distrutti E, Bassotti G, et al: Ef- 33 Ezzeddine D, Jit R, Katz N, Gopalswamy N, 43 Abell T, McCallum R, Hocking M, Koch K,
fect of erythromycin administration on up- Bhutani MS: Pyloric injection of botulinum Abrahamsson H, Leblanc I, Lindberg G,
per gastrointestinal motility in scleroderma toxin for treatment of diabetic gastroparesis. Konturek J, Nowak T, Quigley EM, Tougas
patients. Scand J Gastroenterol 1994;29:807 Gastrointest Endosc 2002;55:920923. G, Starkebaum W: Gastric electrical stimula-
813. 34 Miller LS, Szych GA, Kantor SB, et al: Treat- tion for medically refractory gastroparesis.
24 Ramirez B, Eaker EY, Drane WE, et al: ment of idiopathic gastroparesis with injec- Gastroenterology 2003;125:421428.
Erythromycin enhances gastric emptying in tion of botulinum toxin into the pyloric 44 Forster J, Sarosiek I, Lin Z, et al: Further ex-
patients with gastroparesis after vagotomy sphincter muscle. Am J Gastroenterol 2002; periences with gastric stimulation to treat
and antrectomy. Dig Dis Sci 1994; 39: 2295 97:16531660. drug refractory gastroparesis. Am J Surg
2300. 35 Lacy BE, Crowell MD, Schettler-Duncan A, 2003;186:690695.
25 Richards RD, Davenport K, McCallum RW: Mathis C, Pasricha PJ: The treatment of dia- 45 Lin Z, Sarosiek I, Forster J, McCallum RW:
The treatment of idiopathic and diabetic gas- betic gastroparesis with botulinum toxin in- Symptom responses, long-term outcomes
troparesis with acute intravenous and chron- jection of the pylorus. Diabetes Care 2004; and adverse events beyond 3 years of high
ic oral erythromycin. Am J Gastroenterol 27:23412347. frequency gastric electrical stimulation for
1993;88:203207. 36 Arts J, van GS, Caenepeel P, Verbeke K, Jans- gastroparesis. Neurogastroenterol Motil
26 Samsom M, Jebbink RJ, Akkermans LM, et sens J, Tack J: Influence of intrapyloric botu- 2006;18:1827.
al: Effects of oral erythromycin on fasting linum toxin injection on gastric emptying 46 Anand C, Al-Juburi A, Familoni B, Rashed
and postprandial antroduodenal motility in and meal-related symptoms in gastroparesis H, Cutts T, Abidi N, Johnson WD, Minocha
patients with type I diabetes, measured with patients. Aliment Pharmacol Ther 2006; 24: A, Abell TL: Gastric electrical stimulation is
an ambulatory manometric technique. Dia- 661667. safe and effective: a long-term study in pa-
betes Care 1997;20:129134. 37 Coleski R, Hasler W: Clinical and gastric tients with drug-refractory gastroparesis in
27 Camilleri M: The current role of erythromy- functional predictors of symptom response three regional centers. Digestion 2007; 75:
cin in the clinical management of gastric to pyloric injection of botulinium toxin in 8389.
emptying disorders. Am J Gastroenterol patients with gastroparesis. Neurogastroen- 47 Cutts TF, Luo J, Starkebaum W, Rashid H,
1993;88:169171. terol Motil 2005;17:268. Abell TL: Is gastric electrical stimulation su-
28 Ray WA, Murray KT, Meredith S, et al: Oral 38 Arts J, Holvoet L, Caenepeel P, Bisschops R, perior to standard pharmacologic therapy in
erythromycin and the risk of sudden death Sifrim D, Verbeke K, Janssens J, Tack J: Clin- improving GI symptoms, healthcare re-
from cardiac causes. N Engl J Med 2004;351: ical trial: a randomized-controlled crossover sources, and long-term health care benefits?
10891096. study of intrapyloric injection of botulinum Neurogastroenterol Motil 2005;17:3543.
29 McCallum RW, Cynshi O; US Investigative toxin in gastroparesis. Aliment Pharmacol 48 Ayinala S, Batista O, Goyal A, et al: Tempo-
Team: Efficacy of mitemcinal, a motilin ago- Ther 2007;26:12511258. rary gastric electrical stimulation with orally
nist, on gastrointestinal symptoms suggest- 39 Friedenberg FK, Palit A, Parkman HP, Nel- or PEG-placed electrodes in patients with
ing diabetic gastropathy: a randomized, son D: Randomized, placebo-controlled trial drug refractory gastroparesis. Gastrointest
multi-center, placebo-controlled trial. Ali- of botulinum toxin A for the treatment of de- Endosc 2005; 61:455461.
ment Pharmacol Ther 2007;26:107116. layed gastric emptying. Gastroenterology 49 Elfvin A, Anderson S, Abrahamsson H, et al:
30 Murray CD, Martin NM, Patterson M, et al: 2007;132:M1150. Percutaneous implantation of gastric elec-
Ghrelin enhances gastric emptying in dia- 40 Forster J, Sarosiek I, Delcore R , Lin Z, Raju trodes-a novel technique applied to animals
betic gastroparesis: a double blind, placebo GS, MaCallum RW: Gastric pacing is a new and in patients. Neurogastroenterol Motil
controlled, crossover study. Gut 2005; 54: surgical treatment for gastroparesis. Am J 2007;19:103109.
16931698. Surg 2001; 182:676681. 50 Yin J, Chen JZ: Implantable gastric electrical
31 Sawhney MS, Prakash C, Lustman PJ, Clouse 41 Maranki J, Parkman HP: Gastric electrical stimulation: ready for prime time? Gastro-
RE: Tricyclic antidepressants for persistent stimulation for the treatment of gastropare- enterology 2008; 134:665667.
or recurrent vomiting in diabetic patients. sis. Curr Gastroenterol Rep 2007; 9: 286 51 Ang D, Tack J: Gastric Electrical Stimulation
Gastroenterology 2001; 120:A243. 294. for the treatment of gastroparesis: ready for
32 Bromer MQ, Friedenberg F, Miller LS, et al: 42 Abell TL, Van Cutsem E, Abrahamsson H, prime time? Digestion 2007;75:8082.
Endoscopic pyloric injection of botulinium Huizinga JD, Konturek JW, Galmiche JP,
toxin A for the treatment of refractory gas- Voeller G, Filez L, Everts B, Waterfall WE,
troparesis. Gastrointest Endosc 2005; 61: Domschke W, Bruley des Varannes S,
833839. Familoni BO, Bourgeois IM, Janssens J, Tou-
gas G: Gastric electrical stimulation in in-
tractable symptomatic gastroparesis. Diges-
tion 2002;66:204212.

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