GASTROPARESIS

CAUSES, DIAGNOSIS AND

MANAGEMENT

DR TUHIN MITRA
MODERATOR- DR V K DIXIT
 DEFINITION
OBJECTIVE
EVIDENCE OF
ABSENCE OF
UPPERGASTRIC
MECHANICAL
GI SYMPTOMS
EMPTYING DELAY.
OBSTRUCTION

GASTROP
ARESIS

*Stein et al J Clin Gastroenterol Volume 49, Number 7, August 2015

MOTILITY PHYSIOLOGY – ACCOMODATION
AND EMPTYING
GASTROPARESIS - ETIOLOGY

Lacy B et al. Am J Gastroentero.2018 May;113(5):647-659.

 GASTROPARESIS - ETIOLOGY
In a study of both type 1 and type 2 DM, gatroparesis
was diagnosed in 5% of patients. *

The presence of gastroparesis in patients with

diabetes mellitus is associated with other
complications
 Retinopathy and peripheral neuropathy
 Higher mean levels of HbA1c
 Lower socio-​economic status

*Bytzer, P. et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus.Arch. Intern. Med 2006
GASTROPARESIS - ETIOLOGY
Post surgical gastroparesis

The most common surgical association with

gastroparesis is with fundoplication and bariatric
procedures.
Rarer forms of post-​surgical gastroparesis result from
Billroth I and II gastrectomy ,partial oesophagectomy
for oesophageal cancer.
GASTROPARESIS - ETIOLOGY
MEDICATIONS
The most common iatrogenic associations are with
-μ-opioid agonists.*
-Anticholinergics
-Hypoglycaemic agents such as amylin analogues (for
example, pramlintide) or glucagon-​like peptide 1
(GLP1) analogues or agonists (for example, liraglutide
and exenatide).

 Chronic opioids in gastroparesis: relationship with gastrointestinal symptoms, healthcare utilization and employment.World J.
Gastroenterol
GASTROPARESIS - ETIOLOGY
Gastroparesis has been rarely associated with specific
viral infections
Epstein–Barr virus, norovirus, herpesvirus and
cytomegalovirus.*

 Usually in association with the development of

autonomic dysfunction , with symptoms such as
postural hypotension or abnormal sweating.

 Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis.
Gastroenterology
 EPIDEMIOLOGY
Describing the epidemiology – challenging; overlap with FD

INCIDENCE- 2.4 patients/ 100,000 person-​yrs for men

9.8 patients / 100,000 person-​years fr women

PREVALENCE- 9.6 patients per 100,000 men

37.8 patients per 100,000 women*
*The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006.
Gastroenterology

One study estimated that as many as 1.8% of the general

population may have gastroparesis, but only 0.2% are diagnosed
 EPIDEMIOLOGY
RISKS FACTOR
-Female sex
-Diabetes
-Obesity
*Ravella, K. et al. Chronic estrogen deficiency causes gastroparesis by altering neuronal nitric oxide synthase function. Dig. Dis. Sci. 5

No definite association with cigarette and alcohol

GASTROPARESIS- DIAGNOSIS
CLINICAL SIGNS AND SYMPTOMS
The clinical symptoms of gastroparesis include
 Nausea -41 %
 Vomiting
 Upper abdominal discomfort or pain.-21%
 Bloating -14 to 41% Clustered
 Early satiety Symptoms
 Postprandial fullness

*Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis
severity. Gastroenterology 140, 101–115 (2011
GASTROPARESIS- DIAGNOSIS
INVESTIGATIONS
Patients must first undergo an upper GI endoscopy; if
this test does not reveal a cause for the symptoms.

 Patients can begin functional investigations.

The most relevant functional test is a measurement of
gastric emptying.
 Scintigraphy
 The stable isotope breath test
 Wireless capsule motility test
GASTROPARESIS- DIAGNOSIS
Gastric emptying scintigraphy
It involves the ingestion of a solid meal containing a
radioisotope with short half-​life, 99mT.

Western style meal-the two-​scrambled-egg meal (296

kcal, 30% fat) .

Asian style meals- rice-based meals composed of

steamed rice, a microwaved egg and water (267 kcal:
57% carbohydrate, 23% fat and 19% protein)
GASTROPARESIS- DIAGNOSIS
Gastric emptying scintigraphy
The upper limits of gastric retention at 2 hours and 4 hours
post-​consumption (95th percentile)60% at 2 hours; 10% at 4
hours.
Alternative test meals have been proposed, such as a liquid
nutrient meal (Ensure Plus meal), which has a very similar
gastric emptying profile in healthy participants.

But, these alternative test meals have yet to be clinically

validated in male or female patients with gastroparesis.
 GASTROPARESIS- DIAGNOSIS
The timing of scintigraphy imaging after consumption
of a radiolabelled meal is also of importance.

Data show that imaging up to 4 hours after meal

consumption detects more patients with delayed gastric
emptying than imaging over 90 or 120 minutes.*

*Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility
Society and the Society of Nuclear Medicine. Am
GASTROPARESIS- DIAGNOSIS
Gastric emptying scintigraphy
GASTROPARESIS- DIAGNOSIS
Stable isotope breath test.
The gastric emptying breath test incorporates a stable
isotope, 13C, in a substrate such as octanoic acid or
spirulina platensis (blue-​green algae).

This noninvasive method has similar cost to

scintigraphy, and does not involve exposing patients to
ionizing radiation.
 GASTROPARESIS- DIAGNOSIS
Stable isotope breath test
The principle underlying this test is that the rate of gastric
emptying of the 13C substrate incorporated in the solid meal
is reflected by breath excretion of 13CO2.

The test is conducted over a 4-hour period after an 8-hour

fast.

Pre-​meal breath samples are collected, patients eat a special

test meal and, after consuming the meal, additional
breath samples are collected every 30 minutes.
 GASTROPARESIS- DIAGNOSIS
Stable isotope breath test
The meal empties from the stomach, the medium-​
chain TG (octanoic acid),or the AA’s in spirulina,
rapidly undergo digestion, absorption and metabolism
to produce 13CO2, which is exhaled in the breath.

This test can be falsely negative by malabsorption,

pancreatic exocrine insufficiency ,lung ailments and
exercise.
 GASTROPARESIS- DIAGNOSIS
Wireless motor capsule
WMC has been approved by the US FDA for the
evaluation of gastric emptying .

Once ingested, the WMC measures Ph, temperature

and pressure throughout the GI tract.

The completion of gastric emptying is demonstrated

by an abrupt change in pH into the alkaline range due
to WMC passage into the duodenum.
 GASTROPARESIS- DIAGNOSIS
Wireless motor capsule
Gastric emptying by WMC correlated moderately with
simultaneous gastric emptying of a low-​fat meal
measured by concurrent scintigraphy.

There was only 52.5% agreement with scintigraphy,

and further validation in patients with gastroparesis is
required.*

 Hasler, W. L. et al. Relating gastric scintigraphyand symptoms to motility capsule transit andpressure findings in
suspected gastroparesis.Neurogastroenterol. Motil. 30, e13196 (2018).
GASTROPARESIS- DIAGNOSIS
 GASTROPARESIS- D/D
FUNCTIONAL DYSPEPSIA- A patient with FD can have
delayed or increased gastric emptying, defect in gastric
accomodation or increased visceral sensitivity.

On the basis of the current definition, gastroparesis is

indistinguishable from FD with delayed gastric emptying.

Approximately 25–35% of patients with dyspeptic

symptoms are estimated to have delayed gastric
emptying.*
*Stanghellini, V. et al. Gastroduodenal disorders.Gastroenterology 150, 1380–1392 (2016
 GASTROPARESIS- D/D
Chronic intestinal pseudo obstruction( CIPO)-
The main difference between patients with
gastroparesis and patients with CIPO are episodes
resembling mechanical obstruction.

Other conditions that should be differentiated are

rumination syndrome, cannabinoid hyperemesis
syndrome (CHS) and cyclic vomiting
syndrome(CVS).
GASTROPARESIS - MANAGEMENT
GASTROPARESIS - MANAGEMENT
DIETARY MODIFICATIONS
Dietary modifications represent the first line of
treatment for gastroparesis ,regardless of disease
severity

Oral intake is preferable for nutrition and hydration in

patients with gastroparesis.

* American College of Gastroenterology clinical guideline: management of gastroparesis. Am. J. Gastroenterol. 2013
GASTROPARESIS - MANAGEMENT
DIETARY MODIFICATIONS
As patients often have early satiety, they are
recommended to eat small meals and to avoid foods
high in fat and indigestible fibres.

 Patients are advised to consume liquids such as soups

as the gastric emptying of caloric liquids or
homogenized solids is often preserved in patients with
gastroparesis.*
*American College of Gastroenterology clinical guideline: management of gastroparesis. Am. J. Gastroenterol.
GASTROPARESIS - MANAGEMENT
DIETARY MODIFICATIONS
A study showed,a high-​fat diet with solid meals
increases the severity and frequency of symptoms
among patients with gastroparesis, whereas a small-​
particle-size diet reduces upper GI symptoms in
patients with diabetic gastroparesis.*

*Homko, C. J., Duffy, F., Friedenberg, F. K., Boden, G.& Parkman, H. P. Effect of dietary fat and foodconsistency on gastroparesis
symptoms in patientswith gastroparesis. Neurogastroenterol. Motil.
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY
Medications currently approved
 Metoclopramide
Domperidone
Erythromycin

*McCallum, R. W. & George, S. J. Gastric dysmotilityand gastroparesis. Curr. Treat. Opt. Gastroenterol. 4,179–191
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY-METACLOPRAMIDE
MOA-Metoclopramide (a 5-HT4 agonist and 5-HT3 and
dopamine D2 antagonist) has both prokinetic and anti-​
emetic actions.

DOSE- Metaclopramide 5-10mg bd / tds,,, 10mg

tds/qid,,, Maximum of 12 weeks

ADVERSE EFFECTS- it can cause both acute and chronic

central nervous system side effects in some patients-
depression, anxiety, tremors and tardive
dyskinesia( reversible or irreversible , 1 in 1000)
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY-DOMPERIDONE
MOA- D2 blocker exhibits gastric prokinetic as well as anti-​emetic
properties via action on the area postrema.

Domperidone- 10 mg bd/ tds to 20mg tds

Domperidone does not readily cross the blood–brain barrier; less likely
to cause extrapyramidal s/e.

Domperidone associated with prolongation of the cardiac QTc interval

*Domperidone treatment for gastroparesis:demographic and pharmacogenetic characterization of clinical effi cacy and side-eff ects . Dig Dis Sci 2011
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY- ERYTHROMYCIN
Oral erythromycin,a pure prokinetic agent that acts on
motilin receptors,produced an improvement in
symptoms
A study showed improvement in 43% of patients, but
one-​third of patients experience loss of the long-​term
efficacy of erythromycin due to tachyphylaxis.

Erythromycin - is used off-​label, typically for a short

period of less than a month.Dose-250- 500 mg tds
*Th e treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin . Am J Gastroenterol 1993
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY
Antiemetic agents, including phenothiazines,
antihistamines,and 5-HT3 antagonists are commonly
utilized to treat symptomatic GP patients. However no
RCT to substantiate benefit.

Retrospective data has suggested that TCA may

improve symptoms in those with functional dyspepsia
and in clinical practice these agents have been used to
treat GP. Nortrityline >> amitriptyline
GASTROPARESIS - MANAGEMENT
PHARMACOLOGY- NEW DRUGS
Relamorelin - a ghrelin receptor agonist that stimulates
gastric body and antral contractions, accelerates gastric
emptying , currently undergoing phase 3 trials.

Prucalopride-a 5-HT4 receptor agonist,accelerates

gastric emptying and was shown in a preliminary report
to relieve symptoms in 28 patients with idiopathic
gastroparesis.
* Carbone, F. et al. A controlled, cross- over trial shows benefit of prucalopride for symptom control and gastric emptying
enhancement in idiopathic gastroparesis. Gastroenterology
*Camilleri, M. et al. Efficacy and safety of relamorelin in diabetics with symptoms of gastroparesis: a randomized, placebo- controlled study.
Gastroenterology
GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY
Endoscopic and surgical treatment modalities are
available to eligible patients with recalcitrant GP

The use of interventional treatment options for GP is

limited by modest clinical evidence.
 GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY- PYLORIC INTERVENTION
Some studies showed antral hypomotility and pylorospasm in
patients of GP.

Botulinum toxin-An open-​label study using intrapyloric botulinum

type A (Botox) injection in 179 patients with gastroparesis was
associated with a decrease in gastroparesis symptoms at 1–4 months
in 51.4% pts.

But two double-​blind studies showed no difference in reduction in

of symptoms, compared with placebo
*. Coleski, R Factorsassociated with symptom response to pyloric injectionof botulinum toxin 4, 2634–2642 (2009
*: Acrossover study of intrapyloric injection of botulinumtoxin. Aliment. Pharmacol. Ther. 26,1251–1258 (2007
 GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY- PYLORIC INTERVENTION
Botulinum toxin injections provide temporary relief, lasting
on average 3 months.

 Further studies are necessary to determine the specific

patients who may most benefit from the use of this
treatment.
 GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY- PYLORIC INTERVENTION

Procedures being offered to patients who are refractory to other

treatments-
 Pyloroplasty (to widen the pylorus and prevent spasm)
pyloromyotomy (an incision in the wall of the pylorus by
endoscopic intervention-per-​oral pyloroplasty or gastric POEM

 Reports from open-​label, single-​centre studies have been promising. Clearly, controlled studies are required to assess the efficacy of pyloric interventions.Shlomovitz, E. et al.
Early human experience with peroral endoscopic pyloromyotomy (POP.
GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY- GES
GES involves surgical implantation of an electrode device into the
gastric muscularis, to deliver high frequency, low-energy stimuli.

Chu et al performed a meta-analysis, including 2 prospective

blinded trials and an 8 open, noncontrolled studies, incorporating
a total of 601 GP patients.
Treatment of high-frequency gastric electrical stimulation for gastroparesis. J Gastroenterol Hepatol. 2012;27

The authors found significant overall improvement in symptom

scores and gastric emptying with GES .

The benefit was more with DGP than Idiopathic or post surgical GP
 GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY- GES
 No clear consensus guidelines regarding patient selection for GES.

 GES is most efficacious for patients with DGP /IGP having

intractable nausea and vomiting and with poor nutritional status .
O’Grady G, Egbuji JU, Du P, World J Surg. 2009;33:1693–1701.

Complications related to GES placement are common.

 In a retrospective review of GP patients undergoing GES at a single

institution, Keller et al found that 58% of patients required
additional procedures due to complications after GES placement . 90.
Keller DS, Parkman HP, Boucek DO, et al. Surgical outcomes after gastric electric stimulator placement for refractory
 gastroparesis. J Gastrointest Surg. 2013;17:620–626.
GASTROPARESIS- MANAGEMENT
INTERVENTIONAL THERAPY
Endoscopic or surgical placement of a percutaneous endoscopic gastrostomy tube
used to deliver nutrition -not recommended.

A study showed PEG tubes used to vent and decompress the distended stomach
improved symptom scores in a cohort of 8 women with GP, who sustained an
average 4.5 kg weight gain with ongoing oral feeding over the study’s 12-month
follow-up period. Kim CH, Nelson DK. Venting percutaneous gastrostomy in the treatment of refractory idiopathic gastroparesis. Gastrointest Endosc. 1998;47:67–70.

In nutritionally compromised patients, a direct percutaneous endoscopic

jejunostomy feeding tube may offer maximum nutritive benefit,but will not relieve
symptoms, like nausea and vomiting, associated with a distended stomach.

The relative benefit of gastric venting vs jejunal feeding is yet to be investigated

 GASTROPARESIS-MANAGEMENT
SURGERY
Surgical modalities that alter gastric anatomy may be successful
patients with GP who have failed other, conservative treatment options.

 In a retrospective analysis of outcomes associated with 50 patients with

refractory GP of who underwent laparoscopic pyloroplasty at a single
institution, significant improvement in postoperative symptom severity
(P<0.001) and gastric emptying (P<0.001) at 3 months of follow-up. Toro JP,
Lytle NW, Patel AD, et al. Efficacy of laparoscopic


.
pyloroplasty for the treatment of gastroparesis. J Am Coll Surg. 2014;218:652–660

Subtotal and total gastrectomy is most beneficial in patients with

postsurgical GP associated with damage or transection of the vagus
nerve.
GASTROPARESIS-MANAGEMENT
SURGERY
 Zehetner et al found no significant difference in symptom improvement
between a patients who underwent implantation of GES (N=72) and a cohort of
patients who underwentsubtotal or total gastrectomy (N=31) for the treatment
of refractory GP of mixed etiology. Zehetner J, Ravari F, Ayazi S, et al. Minimally invasivesurgical approach for the treatment of gastroparesis.
Surg Endosc. 2013;27:61–66.

Papasavas et al report significant improvement in individual and total symptom

score at 1 year after Roux-en-Y gastric bypass in 7 obese adults with diabetic and
idiopathic GP, emphasizing the opportunity to treat obesity and symptomatic
GP concomitantly. Papasavas PK, Ng JS, Stone AM, et al. Gastric bypass surgeryas treatment of recalcitrant gastroparesis. Surg Obes Relat Dis. 2014;10:795–799.

 Given that all surgical procedures carry substantial risk of intraoperative and
postoperative adverse events, addittinal studies -clearly define their use in the
treatment of GP
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