GASTROPARESIS

DR.N.ARUN,DNB(Ped),DM(MGE)
Assistant Professor of
Gastroenterology,Annanagar Peripheral
Hospital,Chennai
Consultant Gastroenterologist,Hepatologist &
Interventional Endoscopist,Apollo
Hospitals,Chennai
• Gastroparesis derived from greek “gastro”and “paresis” meaning partial
paralysis of stomach.
• Defined as delayed gastric emptying,in the absence of mechanical
obstruction,associated with one or more of the following symptoms:
-postprandial fullness
-early satiety
-nausea
-vomiting
-bloating
• Defined on basis of objective measurement of gastric emptying.
• Increasing hospital admissions over past decade.
Recommendations

• 1. The diagnosis of gastroparesis is based on the combination of

symptoms of gastroparesis, absence of gastric outlet obstruction or
ulceration, and delay in gastric emptying.

• 2 . Accelerated gastric emptying and functional dyspepsia can

present with symptoms similar to those of gastroparesis; therefore,
documentation of delayed gastric emptying is recommended before
selecting therapy with prokinetics agents or gastric electrical
stimulation (GES).

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

• Definite gastroparesis:
delayed gastric emptying by standard scintigraphy and symptoms of
nausea and/or vomiting,postprandial fullness,early
satiety,bloating,or epigastric pain for more than 3 months.

• Probable gastroparesis:
symptoms as above plus food retention on endoscopy or an upper
gi study,but no scintigraphy has been performed.

• Possible gastroparesis:
typical symptoms alone or delayed gastric emptying by scintigraphy
in the absence of gi symptoms.
BURDEN OF GASTROPARESIS
BURDEN OF GASTROPARESIS

Mortality
• Increasing age and male
gender associated with greater
mortality.
• Nondiabetic gastroparesis
associated with greater
survival.
 PHYSIOLOGY OF GASTRIC FUNCTION
• The three main motile functions associated with digestion in which the stomach
plays a central role include:
• Acts as a reservoir for ingested food
• Mixes food with gastric secretions
• Empties gastric contents into the duodenum

• These motile functions are accomplished by the coordinated movements of three

layers of smooth muscle of the stomach—an outermost longitudinal layer, a
middle circular layer and an innermost oblique layer.

• The longitudinal layer is present only in the distal two-thirds of the stomach,
while the oblique layer is distinguishable only in the proximal half of the
stomach.

• The circular layer is present throughout with maximum thickness in the antrum
where the force of contraction is the greatest.
• Coordination of smooth muscle activity is dependent upon the
enteric neural plexus, especially the myenteric plexus, and the
intensity of contraction depends upon the sympathetic and
parasympathetic efferent neural activity.

• The proximal stomach acts as a reservoir that accommodates to

meal volume by modulating tonic contractile activity.

• The distal stomach generates phasic peristaltic waves of

contraction for mixing, grinding and propelling contents.
 NORMAL GASTRIC EMPTYING
• Normal gastric emptying results from the integration of tonic
contractions of the fundus, phasic contractions of the antrum and the
inhibitory forces of pyloric and duodenal contractions, which requires
complex interactions between smooth muscle, enteric and autonomic
nerves, and specialized pacemaker cells known as the interstitial cells of
Cajal (ICC).
• The emptying of the reservoir is caused by two mechanisms: a tonic
contraction of the fundus and peristaltic waves (phasic contractions)
moving over the distal part of the gastric body and antrum.
• These two forces represent the pump of the gastric reservoir.
• Both the peristaltic waves and the tonic contractions of the reservoir are
stimulated by cholinergic enteric neurons that are under modulatory
vagal tone.
• In the region of the body of the stomach, peristaltic waves only produce
a small circular constriction
• The peristaltic wave originates at the proximal stomach and propagates to
the pylorus.
• Peristaltic waves are based on electrical waves originating in the gastric
wall.
• The pacesetter potential of the ICC drives electrical events in smooth
muscle cells where they are reflected as slow waves.
• Both the pacesetter potentials and slow waves start in the proximal
stomach and move along the syncytium of the smooth muscle cells.
• The pacesetter potentials are always present but do not cause contractions
by themselves.
• Contractions only occur when excitatory neurotransmitters, such as
acetylcholine (ACH), are released.
• In the region of the body of the stomach, the peristaltic waves are shallow,
but when the peristaltic wave reaches the antrum, the circular constriction
becomes deeper.
• The antral pump acts like a sieve.
• As liquids flow more rapidly than viscous and solid materials, liquids
with small suspended particles are swept across the pylorus into the
duodenum, whereas the viscous and solid mass of the chyme is retained
in the stomach.
• The lumen of the antrum is not occluded by the peristaltic wave, and
some amount of chyme flows in a retrograde manner into the relaxing
proximal antrum.
• The phase of emptying overlaps with mixing of the gastric chyme.
Simultaneously, the subsequent peristaltic wave proceeds along the
gastric body, propelling chyme into the proximal antrum.
• Chyme of the gastric body and chyme of the middle antrum accumulate
in the relaxed proximal antrum.
• Contraction of the terminal antrum closes the pylorus, thus
stopping the transpyloric flow.
• The chyme present in the terminal antrum is forced retrograde
across the central opening of the peristaltic wave into the relaxing
middle antrum.
• Forceful mixing of the chyme associated with the grinding of
particles occurs as a result of this jetlike retropulsion.
• Thus, contraction of the terminal antrum denotes the phase of
retropulsion and grinding.
• During the emptying phase of the stomach, the duodenal
contractions are inhibited and the duodenal bulb relaxes. This is
known as antroduodenal coordination
NORMAL GASTRIC EMTYING
NORMAL GASTRIC FUNCTION GASTROPARESIS
PATHOPHYSIOLOGY OF GASTROPARESIS
• Multiple mechanisms at play.
• Despite the definition hinging
on gastric emptying there are
no good data to show that
impaired gastric emptying
causes symptoms
 IDENTIFYING THE CAUSE OF GASTROPARESIS

Recommendations
• 1 . Patients with gastroparesis should be screened for the presence
of diabetes mellitus, thyroid dysfunction, neurological disease, prior
gastric or bariatric surgery, and autoimmune disorders.
Patients should undergo biochemical screen for diabetes and
hypothyroidism; other tests are as indicated clinically.

• 2. A prodrome suggesting a viral illness may lead to gastroparesis

(postviral gastroparesis). This condition may improve over time in
some patients. Clinicians should inquire about the presence of a
prior acute illness suggestive of a viral infection.
• 3 . Markedly uncontrolled ( > 200 mg/d l) glucose levels may
aggravate symptoms of gastroparesis and delay gastric emptying.
Optimization of glycemic control should be a target for therapy; this
may improve symptoms and the delayed gastric emptying.

• 4 . Medication-induced delay in gastric emptying, particularly from

narcotic and anticholinergic agents and glucagon like peptide-1 (GLP-
1) and amylin analogs among diabetics, should be considered in
patients before assigning an etiological diagnosis. Narcotics and other
medications that can delay gastric emptying should be stopped to
establish the diagnosis with a gastric emptying test.

• 5. Gastroparesis can be associated with and may aggravate

gastroesophageal reflux disease (GERD). Evaluation for the presence
of gastroparesis should be considered in patients with GERD that is
refractory to acid-suppressive treatment.

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

 GASTROPARESIS - ETIOLOGY

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

 IDIOPATHIC GASTROPARESIS
• No detectable primary underlying abnormality for the delayed gastric
emptying.
• Most common form of gastroparesis.
• Most patients with IG are women; typically young or middle aged.
• Symptoms of IG overlap with those of functional dyspepsia
functional dyspepsia Idiopathic gastroparesis

Abdominal pain / discomfort nausea, vomiting, early satiety,

and bloating

• Therefore, measurement of gastric emptying is important, as therapies

differ if gastric emptying is delayed, normal, or rapid.
GLUCOSE AND GASTRIC EMPTYING
 DIABETIC GASTROPARESIS
• Delayed gastric emptying was first noted in patients with diabetes and
subsequently reported by Boas in 1925.
• In 1958, the term ‘Gastroparesis diabeticorum’ was coined by
Kassender to describe asymptomatic gastric retention in diabetic
patients.
• DGp affects 20–50% of the diabetic population, especially those with
type 1 diabetes mellitus or those with long-standing ( 10 years) type 2
diabetes mellitus.
• The mean age of onset is approximately 34 years, and prevalence
increases with increasing age.
• Gastroparesis appears to be more common in patients with type 1
diabetes than in those with type 2 diabetes.
• Delayed gastric emptying is found in 27–65% of patients with type 1
diabetes and in up to 30% of patients with type 2 diabetes.
• Prevalence of DGp among patients in a type 1 diabetes case registry was
5% versus 40% in tertiary care centers.
 DIABETIC GASTROPARESIS
• ~5 % among type 1 diabetics, 1 % among type 2 diabetics
• 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

• nutritional compromise
• impaired glucose control
• a poor quality of life,independent of other factors such as age,tobacco
use,alcohol use or type of diabetes.
 Impaired gastric emptying in patients with
diabetes mellitus
• Chronically elevated blood glucose levels - diabetic neuropathy.
• elevated HbA1C - more gi symptoms.
• Acute hyperglycemia may also contribute to motor dysfunction.
• Neurohormonal dysfunction and hyperglycemia reduce the frequency of
antral contractions.
• In contrast,emptying of liquid is usually normal in patients with
hyperglycemia.
• Delayed gastric emptying may be caused or exacerbated by medications for
diabetes incluing amylin analogues and GLP1.
• Delayed gastric emptying has direct effects on glucose metabolism,in
addition to being one means of reducing postpranial hyperglycemia.
• Coexisting psychiatric disorders may also contribute.
 POSTVIRAL GASTROPARESIS
• sudden onset of symptoms after a viral prodrome, suggesting a potential
viral etiology for their symptoms.
• Previously, healthy subjects have developed the sudden onset of nausea,
vomiting, diarrhoea, fever, and cramps suggestive of a systemic viral
infection.
• However, instead of experiencing resolution of symptoms, these
individuals note persistent nausea, vomiting, and early satiety.
Postviral gastroparesis without Postviral gastroparesis with
autonomic neuropathy autonomic neuropathy

cytomegalovirus, Epstein – Barr

virus, varicella zoster
Improves over a period of 1 year May take several years

Better prognosis Worse prognosis

 POSTSURGICAL GASTROPARESIS (PSG)
• vagotomy or vagus nerve
injury
• fundoplication
• Billroth ii gastrectomy
• bariatric surgery that involves
gastroplasty or bypass
procedures.
• Variceal sclerotherapy
• Botulinum toxin injection for
achalasia
• Ablation for atrial fibrillation
• lung or heart transplantation
• Fundoplication - symptoms
suggesting gastric stasis are
extremely common in the first 3
months after fundoplication,
they persist in a minority of
patients at 1 year post surgery.
• Roux-en-Y gastrojejunostomy
predisposes to slow emptying
from the gastric remnant and
delayed transit in the
denervated Roux efferent limb.
(The Roux-en-Y stasis syndrome)
 DIAGNOSIS OF VAGAL INJURY

• Measurement of pancreatic polypeptide in response to modified

sham feeding.
• Normally sham feeding cephalic vagal stimulation
increase in plasma PP of atleast 25pg/ml in the first 20 min followed
by return to baseline.
• Vagal injury – no response
 IATROGENIC GASTROPARESIS
• surgical vagal disruption, which may be due to vagal nerve injury or
intentional vagotomy as part of peptic ulcer surgery.
• Pharmacological agents
 RARE CAUSES

• Other rarer causes Parkinsonism, amyloidosis, and paraneoplastic

disease,scleroderma.
• Mesenteric ischemia should also be considered as a rare cause of
gastroparesis that is potentially reversible.
 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 for 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
• Delayed gastric emptying found in 20-40% patients with FD
26-68% patients with DM
• RISKS FACTOR -Female sex
-Diabetes
-Obesity
• No definite association with cigarette and alcohol
Female > male
• Differences in neuronal nitric oxide synthase (nNOS) dimerization
between females and males have been proposed as a reason for the
female preponderance.
• progesterone effect on gastric emptying.
• In addition, autoimmune disease, which is associated with
gastroparesis, is more common in females.
 DIAGNOSIS OF GASTROPARESIS
Recommendations
1. Documented delay in gastric emptying is required for the diagnosis of
gastroparesis.
Scintigraphic gastric emptying of solids is the standard for the
evaluation of gastric emptying and the diagnosis of gastroparesis.
The most reliable method and parameter for diagnosis of gastroparesis
is gastric retention of solids at 4 h measured by scintigraphy.
2. Alternative approaches for assessment of gastric emptying include
wireless capsule motility testing and 13 C breath testing using
octanoate or spirulina incorporated into a solid meal.
• 3.Medications that affect gastric emptying should be stopped at least 48 h
before diagnostic testing; depending on the pharmacokinetics of the
medication, the drug may need to be stopped > 48 h before testing.

• 4.Patients with diabetes should have blood glucose measured before

starting the gastric emptying test, and hyperglycemia treated with test
started after blood glucose is < 275 mg / dl.

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

• For any type of gastric emptying test, patients should discontinue

medications that may affect gastric emptying. For most medications, this
will be 48 –7 2 h .
• falsely delayed result - narcotic opioid analgesics, anticholinergics
• falsely normal result - metoclopramide, domperidone,erythromycin
• Hyperglycemia (glucose level > 200 m g/d l) delays gastric emptying .
• It is recommended to defer gastric emptying testing until relative
euglycemia (blood glucose < 275 mg /dl) is achieved.
 GASTROPARESIS- DIAGNOSIS

• 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
 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)
• Meal with jam, toast, and water is advocated by the Society of Nuclear
Medicine and The American Neurogastroenterology and Motility Society.
• Asian style meals- rice-based meals composed of steamed rice, a
microwaved egg and water (267 kcal: 57% carbohydrate, 23% fat and 19%
protein).
• The upper limits of gastric retention at 2 hours and 4 hours post-​
consumption : 60% at 2 hours; 10% at 4 hours.
• Assessment of gastric emptying over 4h is necessary.
• Shorter duration solid emptying or sole liquid emptying - lower sensitivity.
• Measurement of liquid gastric emptying, simultaneously or in addition to
solid emptying- increased sensitivity.
• The most reliable parameter to report gastric emptying is the gastric
retention at 4h.
• Gastric emptying T1/2 is also acceptable if imaging has been
performed for 4 h or at least to 50 % emptying.
• However, it is also important to assess emptying at least 1 and 2 h
since prolongation of the early phases of emptying may also be
associated with symptoms of gastroparesis, even though the gastric
retention at 4 h is normal or mildly delayed.
• Gastric emptying T1 / 2 can be quite easily inferred from the linear
interpolation of the data points at 1, 2, and 4h.
 STABLE ISOTOPE BREATH TEST
• The gastric emptying breath test
incorporates a stable isotope, 13C, in a
substrate such as octanoic acid or
spirulina platensis.
• similar cost to scintigraphy
• No radiation exposure.
• principle - 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.
• false negative - malabsorption,
pancreatic exocrine insufficiency lung
ailments and exercise.
 WIRELESS MOTOR CAPSULE
• A WMC that measures pH, pressure, and temperature can assess gastric
emptying by the acidic gastric residence time of the capsule.
• Gastric emptying is determined when there is a rapid increase in the pH
recorded indicating emptying from the acidic stomach to the alkaline
duodenum.
• The gastric residence time of the WMC had a high correlation 85 % with the
T-90 % of gastric emptying scintigraphy , suggesting that the gastric
residence time of the WMC represents a time near the end of the emptying
of a solid meal.
• A 5-h gastric residence time of the WMC was best to differentiate subjects
with delayed or normal gastric emptying based on scintigraphy conducted
simultaneously with sensitivity and specificity of 83 % .
ANTRODUODENAL MANOMETRY
Diagnosis other than gastric emptying:functional lumen
imaging probe(FLIP)
DIFFERENTIAL DIAGNOSIS
 EXCLUSION CRITERIA AND DIFFERENTIAL
DIAGNOSIS
Recommendations
1. The presence of rumination syndrome and / or eating disorders
should be considered when evaluating a patient for gastroparesis.
These disorders may be associated with delayed gastric emptying, and
identification of these disorders may alter management.

2. Cyclic vomiting syndrome (CVS) should also be considered during the

patient history. These patients may require alternative therapy.

3. Chronic usage of cannabinoid agents may cause a syndrome similar

to CVS. Patients presenting with symptoms of gastroparesis should
be advised to stop using these agents.

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

• vomiting vs regurgitation vs rumination syndrome .
Rumination syndrome
• characterized by the repetitive, effortless regurgitation of recently
ingested food into the mouth followed by re-chewing and re-
swallowing or expectorating of food.
• initially described in infants and the developmentally disabled
• widely recognized at all ages and cognitive abilities
• more frequent in females.
• can become a habit, often initiated by a belch, a swallow, or by
stimulation of the palate with the tongue.
• Typically, the effortless repetitive regurgitation occurs within 15 m
in of starting a meal ( vs vomiting from gastroparesis - later in the
postprandial period)
 Eating disorders, such as anorexia and bulimia, can present with
similar presentations.
• The loss of body weight seen in eating disorders can cause a
compensatory delay in gastric emptying.
• Gastric emptying studies in bulimia have yielded conflicting results.
• CVS - When the episodes of vomiting become closer together,
differentiation of “ coalescent” CVS from the more typical daily
symptoms of gastroparesis in an adult can be challenging.
• Typically, gastric emptying in CVS is normal or rapid.
 MANAGEMENT OF GASTROPARESIS

Recommendations
• 1 . The first line of management for gastroparesis patients should
include restoration of fluids and electrolytes, nutritional support
and in diabetics, optimization of glycemic control.

• 2 . Oral intake is preferable for nutrition and hydration. Patients

should receive counseling from a dietician regarding consumption
of frequent small volume nutrient meals that are low in fat and
soluble fiber. If unable to tolerate solid food, then use of
homogenized or liquid nutrient meals is recommended.
• 3. Oral intake is the preferable route for nutrition and hydration. If
oral intake is insufficient, then enteral alimentation by jejunostomy
tube feeding should be pursued (after a trial of nasoenteric tube
feeding).
Indications for enteral nutrition
a. unintentional loss of 10% or more of the usual body weight
during a period of 3 – 6 months
b. repeated hospitalizations for refractory symptoms.

• 4. For enteral alimentation, postpyloric feeding is preferable to

gastric feeding because gastric delivery can be associated with
erratic nutritional support.

• 5 . Enteral feeding is preferable to parenteral nutrition.

Michael Camilleri et al.Clinical Guideline:Management of
Gastroparesis.Am J Gasteroenterol 2013
DIAGNOSTIC FLOWCHART
TREATMENT OPTIONS
GASTROPARESIS - MANAGEMENT
 DIET AND NUTRITIONAL SUPPORT

• Gastroparesis can lead to poor oral intake, a calorie-deficient diet,

and deficiencies in vitamins and minerals .
• The choice of nutritional support depends on the severity of
disease.
• In mild disease, maintaining oral nutrition is the goal of therapy.
• In severe gastroparesis, enteral or parenteral nutrition may be
needed.
• For oral intake - a diet consisting of small meals that are low in fat
and fiber.
• Since gastric emptying of liquids is often preserved in gastroparesis,
blenderized solids or nutrient liquids may empty normally.
 ORAL NUTRITION

• Meals with low-fat content and with low fiber residue.

• Small meal size is advisable because the stomach may only empty an ~ 1 – 2
k cal/ min.
• small, low fat, low fiber meals, 4– 5 times a day
• Increasing the liquid nutrient component of a meal.
• Poor tolerance of a liquid diet is predictive of poor outcome with oral
nutrition.
• High calorie liquids in small volumes can deliver energy and nutrients
without exacerbating symptoms.
• caloric requirement = 25 kcal x current body weight in Kg.
• Carbonated beverages ,Alcohol and tobacco smoking should be avoided.
 ENTERAL NUTRITION
• For patients who are unable to maintain nutrition with oral intake, a feeding
jejunostomy tube, which bypasses the affected stomach, can improve
symptoms and reduce hospitalizations.

• Placement of a jejunal feeding tube, if needed for alimentation, should be

preceded by a successful trial of nasojejunal feeding.

• Occasionally, small bowel dysfunction may occur in patients with

gastroparesis leading to intolerance to jejunal feeding.

• In appropriate patients with normal small bowel function, jejunal feeding

maintains nutrition, relieves symptoms, and reduces the frequency of
hospital admissions for acute exacerbation of symptoms .

• Small intestinal motility/ transit can be assessed before placement of

jejunostomy tube with antroduodenojejunal manometry, WMC, and small
intestinal transit scintigraphy.
• Nutrient feeds are started with diluted infusions and advanced
gradually to iso-osmolar preparations at relatively low infusion rates
(e.g., 20ml/h) increasing to the target infusion rate to support nutrition
and hydration typically to at least 60 ml/ h over 12 –1 5h /d.

• Regulated enteral nutrition may improve glycemic control in diabetic

patients with recurrent vomiting and unpredictable oral intake.

• Complications include infection, tube migration, and dislodgement.

• Enteral feeding should always be preferred over parenteral nutrition.

 GLYCEMIC CONTROL IN DG
Recommendations
• 1. Good glycemic control should be the goal. Since acute
hyperglycemia inhibits gastric emptying, it is assumed that
improved glycemic control may improve gastric emptying and
reduce symptoms.

• 2. Pramlintide and GLP-1 analogs may delay gastric emptying in

diabetics. Cessation of these treatments and use of alternative
approaches should be considered before initiation of therapy for
gastroparesis.

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

 PHARMACOLOGIC THERAPY

Recommendations
• 1 . In addition to dietary therapy, prokinetic therapy should be
considered to improve gastric emptying and gastroparesis
symptoms, taking into account benefits and risks of treatment.

• 2. Metoclopramide is the first line of prokinetic therapy and should

be administered at the lowest effective dose in a liquid formation to
facilitate absorption.
The risk of tardive dyskinesia has been estimated to be < 1 % .
Patients should be instructed to discontinue therapy if they develop
side effects including involuntary movements.
• 3. For patients unable to use metoclopramide, domperidone can be
prescribed in reducing symptoms without the propensity for causing
central nervous system side effects
a baseline electrocardiogram is recommended and treatment withheld if
the corrected QT is >470 ms in male and 450 ms in female patients.

• 4. Erythromycin improves gastric emptying and symptoms from delayed

gastric emptying. Administration of intravenous (IV) erythromycin should
be considered when IV prokinetic therapy is needed in hospitalized
patients. Oral treatment with erythromycin improves gastric emptying
also. However, the longterm effectiveness of oral therapy is limited by
tachyphylaxis.
• 5. Treatment with antiemetic agents should occur for
improvement of associated nausea and vomiting but will not result
in improved gastric emptying.

• 6 . Tricyclic antidepressants (TCA) can be considered for refractory

nausea and vomiting in gastroparesis but will not result in improved
gastric emptying and may potentially retard gastric emptying.

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

 METOCLOPRAMIDE
• 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

• FDA-approved medication for the treatment of gastroparesis for no

longer than a 12-week period.

• The FDA placed a black-box warning on metoclopramide because of the

risk of side effects, including tardive dyskinesia.

• The most common adverse extrapyramidal side eff ects of

metoclopramide are acute dystonias (incidence of 0.2 %).
• The dystonic reactions may be reversed with antihistamines (e.g.,
diphenhydramine), benzodiazepines (e.g., diazepam) or centrally
acting anticholinergic agents (e.g., benztropine).

• associated with corrected QT interval prolongation.

• use of the lowest effective dose for each patient, starting at 5 mg

t.i.d. before meals

• use of the liquid formulation to improve absorption

• facilitate dose titration to a maximum dose of 40 mg / day

• use of “ drug holidays ” or dose reductions.

 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.

• 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
 ERYTHROMYCIN
• acts on motilin receptors.
• tachyphylaxis.
• corrected QT prolongation
• Erythromycin - is used off-​label, typically for a short period of less
than a month.
• Dose-250- 500 mg tds

The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin .
Am J Gastroenterol 1993
 SYMPTOMATIC TREATMENT OF NAUSEA,
VOMITING, AND PAIN

• The most commonly prescribed antiemetic drugs are the phenothiazines

(including prochlorperazine and thiethylperazine) or antihistamine agents
(including promethazine).
• 5-HT 3 -receptor antagonists are reasonable second-line medications.
• The synthetic cannabinoid, dronabinol (risk of hyperemesis on withdrawal).
• Transdermal scopolamine
• Acupuncture
• Tricyclic antidepressants
• Management of pain is challenging.(Agents used in practice are not based
on evidence of efficacy for pain).
• TCA,SSRI – depression in diabetes.
• TCA in low doses may decrease symptoms of nausea, vomiting, and
abdominal pain.
• Amitriptyline - anticholinergic effects ,delay gastric emptying.
• Nortriptyline has lower incidence of anticholinergic side effects than
amitriptyline.
• The 5-HT 2 receptor antagonist, mirtazapine.
• narcotics should be stopped (worsen gastric emptying and may
themselves induce symptoms of nausea and vomiting).
• Tramadol, tapentadol, gabapentin, pregabalin, and nortriptyline
may be alternatives for pain; however, their effect on gastric
emptying is still unclear.
 NEWER DRUGS
• NK1R antagonists - aprepitant,traipitant
• Ghrelin agonist -relamorelin
• Relamorelin - a ghrelin receptor agonist that stimulates gastric body
and antral contractions, accelerates gastric emptying , currently
undergoing phase 3 trials.
• 5HT4 agonists – prucalopride,velusetrag
• 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
 INTERVENTIONAL THERAPY

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.
 INTRAPYLORIC BOTULINUM TOXIN INJECTION
Recommendations
• Not recommended based on randomized controlled trials.

• Manometric studies of patients with DG show prolonged periods of increased pyloric

tone and phasic contractions, a phenomenon termed as
“ pylorospasm. ”

• Botulinum toxin is a potent inhibitor of neuromuscular transmission.

• Two double-blind, placebo-controlled studies have shown some improvement in gastric

emptying, but no improvement in symptoms compared with placebo.

• Thus, botulinum toxin injection into the pylorus is not recommended as a treatment for
gastroparesis ,although there is a need for further study in patients with documented “
pylorospasm. ”

*. 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
 GASTRIC ELECTRICAL STIMULATION
Recommendations
1. GES may be considered for compassionate treatment in patients with refractory
symptoms, particularly nausea and vomiting.
Symptom severity and gastric emptying have been shown to improve in patients with
DG, but not in patients with IG or PSG.

• GES delivers high frequency (several fold higher than the intrinsic gastric electrical
frequency), lower energy electrical stimulation to the stomach.

• The device was approved by the FDA as a humanitarian device exemption in patients
with refractory symptoms of gastroparesis of diabetic or idiopathic etiology in 2000
based on two studies .

• review of the literature indicate that further controlled studies are required to confirm
the clinical benefits of high frequency GES.

• In general, efficacy for symptomatic improvement appears to be greater for DG than for
IG.
• Complications from the device
-local infection, lead migration.
• complications related to the
surgery-10%.
• No consensus on selection of
patients.
 SURGICAL TREATMENTS
• VENTING GASTROSTOMY, GASTROJEUNOSTOMY, PYLOROPLASTY, AND
GASTRECTOMY

Recommendations
1. Gastrostomy for venting and / or jejunostomy for feeding may be performed
for symptom relief.

2. Completion gastrectomy could be considered in patients with PSG who

remain markedly symptomatic and fail medical therapy.

3. Surgical pyloroplasty or gastrojejunosotomy has been performed for

treatment for refractory gastroparesis.

4. Partial gastrectomy and pyloroplasty should be used rarely, only in carefully

selected patients

Michael Camilleri et al.Clinical Guideline:Management of Gastroparesis.Am J Gasteroenterol 2013

 COMPLEMENTARY AND ALTERNATIVE
MEDICINES
Recommendations
• Acupuncture can be considered as an alternative therapy. This has
been associated with improved rates of gastric emptying and
reduction of symptoms. (Conditional recommendation, low level of
evidence)
THANK YOU