GastroparesisAetiology, Assessment and Management

Dr Asma Fikree BMBCh, MRCP, PhDConsultant Gastroenterologist

Barts Health NHS Trust

BAPEN26.11.19

Neurogastroenterology Group

Conflicts of interest: none

Overview

1. Definitions

2. Differential diagnosis of gastroparetic symptoms

3. Causes of delayed gastric emptying

4. Tests for gastroparesis

5. Management – biopsychosocial

Gastroparesis Diabeticorum :

1958: 21 cases

2019: 5 million US individuals

Epidemiology of gastroparesis

Wang, AM J Gastro, 2008: 313-322 Hyett, Gastroenterology, 2009:445-52

Gastroparesis: current definition

1. Delayed gastric emptying

2. Absence of mechanical obstruction

3. Typical symptoms

Symptoms of gastroparesis

• Nausea• Vomiting• Early satiety• Postprandial fullness• Bloating• Abdominal pain1

Dyspepsia

Severity of symptoms poorly related to severity of gastric emptying

•Severe in 1/3•F>M•Associated with:

•Opiates•Somatisation•Depression, anxiety•NOT gastric emptying time

1:Parkman, Dig Dis Sci, 2018

Gastroparesis?

Delayed gastric emptying

Absence of mechanical obstruction

Typical dyspeptic symptoms

Gastroparesis

Functional dyspepsiaCyclical vomitingAnorexia NervosaOpiate use

Gastroparesis mimics:

• Functional GI disorders• Functional dyspepsia – postprandial distress syndrome: 30% have

delayed GE• Functional nausea• Functional vomiting

• Rumination: HRM-Z• Cannabinoid hyperemesis syndrome• Cyclical vomiting: FH or PMH migraines• Opiates• Psychological issues

• Eating disorders: anorexia nervosa, bulimia nervosa, ARFID• Stress/anxiety

Gastric physiology made easy

Accommodation -vagus

Gastric pacemaker :ICC3 contractions/min

Gastric sensitivityTension receptors

Gastric contractilityVagus

Gastroparesis:

Gastric contractilityVagus

GASTROPARESIS

Functional dyspepsia:

Gastric sensitivityTension receptors

FUNCTIONAL DYSPEPSIA

Copyright © Society of Nuclear Medicine and Molecular Imaging

Impaired fundic accommodation in dyspepsia

Perry , J Nucl Med , 2018:691-697

Causes of delayed gastric emptying/gastroparesis

• Diabetes:– T1>T2– Microvascular

complications– Higher HbA1c

• Post surgical: – Billroth gastrectomy– Oesophagectomy– Bypass surgery– Fundoplication

• Idiopathic

• Connective tissue disorders

– Systemic sclerosis, SLE

– hEDS

• GI neuromuscular disorders

• Parkinsons, MS, Myotonic dystrophy

• Autonomic dysfunction

• Viruses: EBV, CMV, Norovirus, Herpes

• Drugs:

– Opiates

– Anticholinergics

– Antipsychotics

– Liraglutide, but not gliptins

• Renal failure

• Pregnancy

• Anorexia Nervosa, Very low BMI

• Functional dyspepsia

• Iatrogenic

Assessment of gastric emptying

Assessment of gastric emptying – breath test

NormalAcceleratedDelayed

Assessment of gastric emptying - scintigraphy

Assessment of gastric emptying – smart pill

Management of gastroparesis

Management principles

• Biopsychosocial• Multidisciplinary

• Gastro• GI surgeon• Dietician/nutrition team• Psychology/psychiatry• Diabetes• GP• Nursing staff

• Rule out other diagnoses, including psychiatric ones• Stop drugs which delay gastric emptying eg opiates

• 3 prong approach:1. Treatment of complications2. Treatment of underlying aetiology3. Treatment of symptoms

Treatment of complications

• Nutritional problems

• NJ/PEG-J/surgical jejunostomy

• Consider possibility of eating disorder

• Electrolyte deficiencies

• Dehydration

Treatment of underlying cause

• Constipation

• Psychology

• Diabetes

• Opiates

Special cases - DM

• Delayed GE present in 27–65% T1 and 30% T2

– Unlikely if no microvascular complications

– Makes BM control very difficult postprandially

– Continuous BM monitoring and insulin pumps are helpful

– After 24 weeks of treatment: • More time in euglycaemia, less time in hypo and hyperglycaemia

• Significantly less nausea, vomiting, early satiety, postprandial fullness, bloating

• Improved liquid nutrient meal tolerance 420 to 480ml

Calles-Escandon, Plos one, 2018: e0194759

• 223 patients with gastroparesis • 20% regular opiates, 10% prn opiates• Median morphine equivalent: 60mg per day

• Patients on opiates:• More intense and long-lasting nausea• More vomiting episodes which were also more severe• More retching, heartburn, chest discomfort, upper abdominal pain• Increased hospitalisation

Treatment of symptoms

• Diet

• Drugs:

– Prokinetics

– Antiemetics

– Antidepressants - Mirtazapine

– Other

• Venting gastrostomy

• Gastric electrical stimulation

• Pyloric interventions:

– Pyloric botox

– Pyloroplasty

Dietary management

• Graze

• Low fibre, low fat

• Liquid easier than solid –blenderized food

• Liquid supplements

Olauuson et al, Am J Gastroenterol, 2014: 375-385

Small particle diet

Low glycaemic diet

Management: Prokinetics

Metoclopromide 10mg tdsTardive dyskinesia, tremors

Domperidone 10-20mg tdsIncr QT intervalIncreased PL

Erythromycin 100 tds or 250mg bdTachyphylaxis, no more than 1 month

Prucalopride 1-2mg odAlso improves constipation

• N=13• 250mg tds vs 10mg tds for 3 weeks• Reduction in GE time in both groups• Reduction in symptoms in both, but more in

erythromycin

Management : antiemetics

Prochlorperazine (Stemetil):PhenothiazinePO: 5-10mg tdsBuccal: 3mg bdPR: 25mg tds

Promethazine (Phenergan):antihistamine, sedatinggood for urticaria and anxiety25mg nocte

Ondansetron: 5HT3 antagonist4-8mg tds PO/meltsconstipation, prolongs QT interval

Aprepitant :NK1 agonist125mg od

Cyclizine :anticholinergic, antihistamineworsens gastric emptying

Nausea

Vomiting

Retching

Management - mirtazapine

• 15-45mg od

• Improves:• Anorexia• Nausea• Nutrient tolerance• ? Gastric emptying• Mood

• Side effects:• Weight gain• Drowsiness• Suicidal tendencies

Malamood, Drug Des. Devel. Ther; 2017: 1035-1041

Management – others

Buspirone Relamorelin• Ghrelin agonist

• S/C dose bd

• Accelerates gastric emptying

• No change in vomiting

• Improves nausea, pain , fullness, bloating

Tack, CGH, 2012: 1240-1245

• Anxiolytic and 5HT1A agonist• 10mg tds• Improves gastric accommodation• Side effects:Dizziness

Camilleri, Gastro, 2017, 1240-1250

Management – venting gastrostomy

• Refractory patients, n=8

• Vent 5-6 times per week

• Longer duration of PEG if anxiety /depression

• 6/8 returned to school/work

• Prokinetics discontinued in all

Kim, Gastrointest Endoscopy, 1998, 67-70

Pyloric Botox

• Short lasting

• Better response in: 2

– Women, <50, pylorospasm,idiopathic

• Second injection: 73% response

• ? Predicts efficacy of pyloroplasty

1:Arts, APT, 2007: 1251-1258 2: Coleski Dig Dis Sci, 2009. 2634-2642

Pyloroplasty and G-POEM

• Several open label studies• Refractory patients• Improved gastric emptying in most• Symptoms do not improve as much• Complications: pyloric ulcers

• No guidelines• May be more effective in :

• Pylorospasm• Reduced pyloric compliance• Effective Botox• Refractory patients

Gastric electrical stimulation

• Sensory interference

• Studies are mixed

• Open label studies:

– Improvement in Sx, nutrition

– Better response if:

• N and V

• Diabetes

• Absence of opiates

• Meta-analysis of RCTs :– NO significant change in Sx in ON vs OFF

• Need MDT decision incl psych

• Complications: • Device migration• Pain at implantation site• Lead displacement• Bowel obstruction• Erosion through skin (partic in hEDS)

Zoll, J Clin Outcomes Manag , 2019, 27-38

hEDS: gastroparetic type symptoms

• High prevalence of FGID in hEDS1

– Strong association with Functional Dyspepsia – PDS

• Weight loss multifactorial 2

• High prevalence of :

• Chronic pain syndromes

• Psychopathology including eating disorders

• Biopsychosocial assessment and management is critical

• Feeding tubes can be associated with pain, complications and failure

1Fikree, NGM, 2015, 2 Baeza Velasco; Eat weight Disorders; 2016

Summary:

• Delayed gastric emptying is not synonymous with gastroparesis

• Gastroparesis is not a diagnosis –the gastric emptying delay may not explain

symptoms – describe symptoms and severity of delay

• Severity of symptoms is poorly correlated with severity of gastric emptying

delay

• A good history is essential to rule out mimics

• Many factors can delay GE: low BMI, opiates, high BM’s, anticholinergics

• Management is biopsychosocial –involve MDT team in refractory cases,

consider psychosocial aspects

• Management :

• Treat symptoms: diet, drugs, GES, pyloric botox

• Treat complications

• Treat cause where possible

Useful resources/reviews

Camilleri et al, Nat Rev Dis Primers, 2018, 41

Good review of gastroparesis

Fosso, Quigley. Gastroenterol Hepatol. 2018: 140-45

Discussions about validity of gastroparesis diagnosis

Zoll et al, J Clin Outcome Manag, 2019, 27-38

Review of studies of gastric electrical stimulation