modern management of gastroparesis
TRANSCRIPT
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Modern Management of Gastroparesis
Edy E Soffer, M.D.yCenter for Digestive Diseases
GI Motility programCedars-Sinai Medical center
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Obj tiObjectives
• Physiology of gastric motor function
• Epidemiology
• Evaluation
• Treatment options• Treatment options
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ICC’s
Vagus,
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Vagal dysfunction
Hyperglycemia
▼ NO, VIPPoor accomodation
Pyloric spasm
▼ ICC’s, Dysrhythmia
Weak contractions
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Patterns of Gastric Emptying in Healthy People and in Patients with Diabetic Gastroparesis
Camilleri M. N Engl J Med 2007;356:820-829
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GASTROPARESIS (N=146)
Misc
Con. Tis. Dis.
Misc.
Idiopathic35.6%4 8%
6%
Pseudobs 4.1%4.8%
Di b ti
Par. Dis.
29%
7.5%
DiabeticPost-gastric
29%13%
Soykan I et al.; Dig Dis Sci 1998.
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Gastroparesis: Epidemiology
• Prevalence: 24.2 In Olmstead county C h 133 UC 229Crohns-133, UC-229 (Jung, Gastroenterology (200)
• More prevalent in females• Increasing with age (Gastroparesis Concortium, DDW
2010)
• Heavy health cost burden (W A J G 2008)• Heavy health cost burden (Wang, Am J Gastro 2008)
• Long-standing, poorly controlled type II and long standing type 1 DM multi organand long standing type 1 DM, multi-organ involvement
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Gastroparesis: Symptoms
• Early satiety, postprandial nausea or vomiting, bloating, abdominal pain, weight loss
• The result of dysfunction of various gastric segmentsgastric segments
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Gastroparesis: Evaluation
• History and physicalE l d i l i• Exclude organic lesions:– Obstructive: KUB,EGD,
SBFT CTSBFT, CT– Drug related
CNS– CNS– Pregnancy!
• Gastric emptying study
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Lin HC, Dig Dis Sci 2005
t 1/2
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Normal values for low-fat, Gastric emptying Scintigraphy
L li it Upper limit
1 hr 30% * 90%
Time Lower limit gastric retention
Upper limit gastric retention
1 hr 30% 90%
2 hr 60%
4 hr 10%
t1/2 (in Minutes) 132
V l 95 til fid i t l
•* Consistent with rapid emptying
• 4 hr value increases the detection of
Values, 95 percentile confidence interval
gastroparesis, more reproducible•Cremonini F, Aliment Pharmacol Ther 2002
Tougas G, Am J Gatroenterol 2000
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Treatment Principles
• Reduce symptomsReduce symptoms• Rectify causes of gastroparesis
(medications) control aggravating factors(medications), control aggravating factors (glucose control)N t iti l t t / t• Nutritional status/support
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Management of Gastroparesis
• Dietary modification, Glucose control(l ti i li i t 2 l t d(long acting insulin in type 2 on oral agents, and in type 1 to minimize postprandial swings in blood glucose, insulin pump, post prandial short
i i li )acting insulin)• Medications: antiemetics, promotility• Pain control• Pain control• Nutritional support: enteral, TPN• Surgery: feedeng tubes, gastric electrical g y g , g
stimulation (GES)
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Management of Gastroparesis: DietManagement of Gastroparesis: Diet
• Small frequent mealsSmall frequent meals• Low fat (liquid fat)• Mechanically soft pureed liquid• Low residue• Supplementation: vitamins
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Management of Gastroparesis: Antiemetics
• Phenothiazines: prochloperazine, promethazine.Phenothiazines: prochloperazine, promethazine.• Dopamine antagonists: metoclopramide (10 mg
QID) domperidone ( up to 20mg qid) DomperidoneQID), domperidone ( up to 20mg qid). Domperidone requires IND and IRB approvalS t i 3 t i t d t (4 8 TID)• Serotonin 3 antagonists: ondansetron (4-8 mg TID)
• Cannabinoid: Dronabinol (5-10 mg BID)
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Management of Gastroparesis: Promotility
• Dopamine antagonists: metchlopramideDopamine antagonists: metchlopramide, domperidone
• Erythromycin (2-3 mg/Kg TID)
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Antiemetics/prokinetics : Adverse Effects
• Metochlopramide: fatigue , mood change, EPS, tardive dykinesia. recent “black box” label (TD, 1:17,800 to y (1:35,000 prescriptions. Rao AS, APT 2010)
• domperidone:▲ prolactin, gynecomastia, galactorrhea. Good safety profile due to poor penetration of blood brainGood safety profile due to poor penetration of blood brain barrier
• Erythromycin: Risk of sudden death due to drug interaction (NEJM, 2004)
• Phenothiazines: sedation, orthostatic hypotension, EPS
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Management of Gastroparesis: Medications
• Adequate dosing (strength, frequency)dequ e dos g (s e g , eque cy)• Adequate mode of delivery (ODT,
liquid suppository J-tube)liquid, suppository, J-tube) • Combination therapy
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Management of Gastroparesis: Alternative N t itiNutrition
Jejunostomy-tube feeding:Jejunostomy tube feeding:
• Simple to operate (pump), cheap, i i l bidiminimal morbidity
• Improves nutritional status, glucosep , gcontrol, reduces hospitalizations
TPN: expensive risky difficult toTPN: expensive, risky, difficult to operate
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GES for Gastroparesis
• Improvement in symptoms, QOL p y p , Q(open label studies)
• Improved nutritional status Abell T, JPEN 2002p• Reduced costs and healthcare utilization. Abell T,
Neurogastro 2005
d l l• Improved glucose control Lin Z, Diabetes care 2004
• Open label studies reported good clinicalOpen label studies reported good clinical response Soffer E, APT 2009
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Gastric Electrical Stimulation: Current Stat s/IndicationsStatus/Indications
• HDE status requires IRB• HDE status, requires IRB
• Diabetic and idiopathic gastroparesis
• Chronic, not responsive to available therapy, particularly when alternative nutrition required
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Gastric Electrical Stimulation: Complications
• Device infection ~ 5-10%
• Device migration
S h ll f i• Stomach wall perforation
• Abdominal painp
• In most patients device can be reimplanted
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Gastric Electrical Stimulation:Gastric Electrical Stimulation:My Take
• Patient selection!!-- what are the symptoms?y p-- poor predictors: Idiopathic gastroparesis,
pain/psychiatric ?pain/psychiatric ?-- Diabetic control
• Maximize Rx prior to implantation /• Maximize Rx prior to implantation / consider enteral feeding
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Lacey B et al, Diabetes care, 2004, 10:2341
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BOTOX in Gastroparesisp
• Data on symptoms and gastroparesis: o sy p o s d g s op es s:inconclusiveR k bl ff t i l ti ti t• Remarkable effect in selective patients
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What is in the pipe line?
• Ghrelin analog-TZP-101• AzithromycinAzithromycin• Velustrag- 5HT4 agonit