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When Mr. Creosote Meets the Wafer-Thin Mint
GASTROPARESISPatricia L. Raymond MD FACG Rx For Sanity, Norfolk VA Assistant Professor of Clinical Internal Medicine, Eastern Virginia Medical School
1983
Mr Creosotefrom Monty Python's The Meaning of Life, 1983
on YouTube at https://youtu.be/aczPDGC3f8U and https://youtu.be/lhbHTjMLN5c?list=RDrXH_12QWWg8
etiology of gastroparesisN=146 patients 36% idiopathic (23% post viral, perhaps enterovirus) (9 of 11 IGP patients had active enterovirus infection, treatment trials IVIG. Barkin, U Miami, Abstract, ACG 2015) 29% diabetic 13% post gastric surgery 7.5% Parkinson's disease 4.8% collagen vascular disorders 4.1% intestinal pseudoobstruction 6% miscellaneous causes (malignancy, medications) Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Soykan I, Sivri B, Sarosiek I, et al. Dig Dis Sci. 1998;43(11):2398.
•Many sources list idiopathic as 50% of all gastroparesis
diabetic gastroparesis• diabetics over 10 years duration
• type 1: 5% • more severe than type 2 gastroparesis
• type 2: 1% Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population. Choung RS, Locke GR 3rd, Schleck CD,et al. Am J Gastroenterol. 2012 Jan;107(1):82-8. Epub 2011 Nov 15.
• Neuropathy • Glucose control
• >200, slow. Fast=fast
post surgical gastroparesis•both gastric and thoracic surgery lead to injury to the vagus nerves
•Billroth II gastrectomy, fundoplication, lung or heart transplantation, ablation for atrial fibrillation
•62.9 % of lung transplant patients have GP; may induce aspiration, bronchiolitis obliterans, and transplant failure
•(Stanford abstract ACG 2015) •variceal sclerotherapy •botulinum toxin injection for medical treatment of achalasia •roux stasis syndrome (after a Roux-en-Y anastomosis)
•uncoordinated contractions in the efferent Roux limb itself causes stasis either in the gastric remnant or in the Roux limb itself
Stasis syndromes following gastric surgery: clinical and motility features of 60 symptomatic patients. Fich A, Neri M, Camilleri M, et al.J Clin Gastroenterol. 1990;12(5):505.
Acute reversible gastroparesis and megaduodenum after botulinum toxin injection for achalasia. Radaelli F, Paggi S, Terreni N, Toldi A, Terruzzi V Gastrointest Endosc. 2010;71(7):1326.
sidebar: diagnosis of vagal injury
• measurement of the plasma pancreatic polypeptide (PP) response to modified sham feeding
– normal physiology: sham feeding (chewing but not swallowing food) results in cephalic vagal stimulation and thereby a rapid increase in plasma PP of at least 25 pg/mL in the first 20 minutes followed by a return to baseline
– vagal injury: sham feeding causes no increase in PP over baseline
symptoms of gastroparesis
• nausea (93 percent) • vomiting (68 to 84 percent)
• may include food several hours old • abdominal pain (46 to 90 percent)
• upper abdomen • burning, vague, or crampy
• 60 percent report exacerbation of pain after eating
• early satiety (60 to 86 percent) • also postprandial fullness, bloating, weight loss
succussion splash• a sloshing sound heard through the stethoscope during
sudden movement of the patient on abdominal auscultation
• elicited by placing the stethoscope over the upper abdomen and rocking the patient back and forth at the hips
• retained gastric material greater than three hours after a meal will generate a splash sound and indicate the presence of a hollow viscus filled with both fluid and gas
https://youtu.be/usyjKLQtl_w
egd to exclude
• Pyloric stenosis or stricture • Pyloric channel ulcer
pyloric cancer
egd findings suggestive of gastroparesis
• bezoar –trichobezoar “Rapunzel
syndrome” –phytobezoar
Utility of upper endoscopy as a diagnostic tool in symptomatic patients with gastroparesis. UMissouri abstract, ACG 2015
Gastric Bezoar Treatment by Endoscopic Fragmentation in Combination with Pepsi-Cola® Administration. Iwamuro M, Yunoki N, Tomoda J, Nakamura K, et al. .Am J Case Rep. 2015 Jul 10;16:445-8. doi: 10.12659/AJCR.893786.
specificity of retained food on EGD for dx GP is 90%
assess gastric emptying
• scintigraphy • wireless capsule motility • change in pH between stomach and small bowel indicates the gastric emptying time for a nondigestible solid >1 cm long
• compared with scintigraphy, WMC had a sensitivity of 59 to 86 percent and specificity of 64 to 81 percent
Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Kuo B, McCallum RW, Koch KL, et al. Aliment Pharmacol Ther. 2008;27(2):186.
• rare testing: EGG (electrogastrogram), MRI, US, isotope breath testing
scintillating scintigraphy every hospital has
own technique and normal values • oatmeal, egg salad, beef stew
– technetium-99
• cannot compare between hospitals
• some do both solid and liquid phase emptying
if not gastroparesis…• psychiatric
• depression or anxiety • eating disorders (anorexia nervosa, bulimia) • psychogenic vomiting
•rumination syndrome • highly stressed, high achievers, or
perfectionists • daily, effortless regurgitation of undigested
food within minutes of starting or completing ingestion of a meal
• no nausea or heaving
Rumination syndrome: an emerging case scenario. Attri N, Ravipati M, Agrawal P, et al. South Med J. 2008;101(4):432. http://www.amusingtime.com/images/043/cow-funny-face-picture-for-facebook.jpg
if not gastroparesis…(2)• cyclic vomiting syndrome (CVS)
• recurrent episodes of intense nausea and vomiting lasting hours to days separated by symptom-free periods of variable lengths.
• rapid gastric emptying in some patients when between cycles
• cannabinoid hyperemesis syndrome • may look like CVS • improved with hot showers and baths
Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Allen JH, de Moore GM, Heddle R, Twartz JC. Gut. 2004;53(11):1566.
Cannabinoid hyperemesis syndrome video
treatment options
• diet • medications • antiemetics and prokinetics • electrical stimulators (“pacemakers”) • alteration of pylorus • surgery
general treatment for all•avoid carbonated beverages •avoid alcohol and smoking
•decrease antral contractility and delay gastric emptying •pay attention to hydration despite vomiting
•WHO oral rehydration solution •chewable or gummy vitamin supplementation
•low intake below RDA of vitamins B6, vitamin C, folate, niacin, riboflavin, thiamine, calcium, copper, iron, magnesium, phosphorus, & zinc
•22% low in 1 or more: B1, B6, B12, D, folate, zinc or CoQ10 •(Abstract ACG 2015)
•optimize glycemic control if diabetic Smoking delays gastric emptying of solids. Miller G, Palmer KR, Smith B, et al. Gut. 1989 Jan;30(1):50-3.
Idiopathic gastroparesis is associated with a multiplicity of severe dietary deficiencies. Ogorek CP, Davidson L, Fisher RS, Krevsky B Am J Gastroenterol. 1991;86(4):423.
take a hike
• postprandial walking • 50 patients with DM
• Emptying rates of 28 patients (56%) were within normal range of controls
• 4 patients with accelerated emptying (8%).
• 18 patients with delayed emptying (36%)
Lipp, R. W. American Journal of Gastroenterology 2000; 95(2), 419–424.
postprandial walking• two variants of delayed
gastric emptying (18 of 50 patients):
• counteracted by postprandial walking in 7 patients (39% of GP)
• not influenced by postprandial walking in 11 patients (61% of GP)
small particle size dietAm J Gastroenterol. 2014 Mar;109(3):375-85. doi: 10.1038/ajg.2013.453. Epub 2014 Jan 14. A small particle size diet reduces upper gastrointestinal symptoms in patients with diabetic gastroparesis: a randomized controlled trial. •56 subjects with insulin treated DM and gastroparesis were randomized to the intervention diet or the control diet. The patients received dietary advice by a dietitian at 7 occasions during 20 weeks. GI symptom severity, nutrient intake and glycemic control were measured before and after the intervention.
RESULTS: A significantly greater reduction of the severity of the key gastroparetic symptoms-nausea/vomiting (P=0.01), postprandial fullness (P=0.02) and bloating (P=0.006)-were seen in patients who received the intervention diet compared with the control diet, and this was also true for regurgitation/heartburn (P=0.02), but not for abdominal pain.
medications
• prokinetics • erythromycin or azithromycin • metaclopramide (reglan) • cisapride • domperidone
• antiemetics (ginger, sea-bands, phenergan, ondansetron)
erythromycin
• erythromycin – 3mg/kg IV q 8 hours over 45 min to ‘kick-start’ stomach
• High amplitude gastric propulsive contractions which dump solid residue out of stomach
• slow infusion to avoid sclerosing veins – evidence for po Erythro weak
• 35 trials, only 5 ‘fulfilled inclusion criteria’, all small #,all short (< 4 weeks)
• improvement in 26 of 60 patients (43%)
Prather, CM. Am J Physiol 1993; 264:G928. Keshavarzian, A. Am J Gastroenterol 1993; 88:193. Maganti, K. Am J Gastroenterol 2003; 98:259.
tachyphylaxis
• erythromycin use > several weeks associated with tachyphylaxis due to downregulation of the motilin receptor
• clinical responsiveness drops after 4 weeks of oral erythromycin
• some patients may continue to experience benefit
(acute rapid decrease in response to a drug after its administration)
erythromycin potential side effects
• gi toxicity • ototoxicity • c. difficile colitis • sudden death due to
prolonged QT interval • EKG, interval unclear
• azithromycin is bioequivalent
Azithromycin for the treatment of gastroparesis. Potter TG, Snider KR. Ann Pharmacother. 2013 Mar;47(3):411-5. doi: 10.1345/aph.1R541. Epub 2013 Feb 27. Review.
reglan/metaclopramide
• po or sq – irritability, anxiety, depression, hyperprolactinemia – tardive dyskinesia
• Continuous and repetitive movements of the mouth, tongue, and jaw• Facial grimacing• Lip smacking• Puffing of the cheeks• Uncontrollable movements of the arms, legs, fingers, and toes• Swaying motions of the trunk or hips
– 2010 meta analysis UK & Sweden tardive dyskinesia <1%, may be reversible if caught early
Rao, AS. Aliment Pharmacol Ther 2010; 31:11.
reglan/metaclopramide po: start low, give holidays
• 5mg 15 minutes AC and HS
• titrate upward (to 40 mg/day), lowest possible dose
• use liquid version, SQ for better delivery
• drug holidays or occasional dose reductions
• notify medical team for any involuntary movement
• early recognition and drug discontinuation may lead to resolution
cisapride & tegaserod: we wish
• cisapride (propulsid): QT interval issues with cardiac arrhythmias and death –5HT3 receptor agonist –increased solid and liquid emptying in
various gastric stasis conditions –more potent and better tolerated than reglan
• tegaserod (zelnorm) • 5HT4 receptor agonist (IBS-C)
domperidone
• not FDA approved for use in the US –can be obtained through IND application
• may be purchased overseas by internet –efficacy similar to metaclopramide –cardiac arrhythmias in animal studies
• advise baseline and treatment EKG – withhold for QT>470 men and >450
womenDomperidone safety: a mini-review of the science of QT prolongation and clinical implications of recent global regulatory recommendations. Buffery PJ, Strother RM. N Z Med J. 2015 Jun 12;128(1416):66-74. Review.
domperidone“domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers”
“limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk”
Domperidone safety: a mini-review of the science of QT prolongation and clinical implications of recent global regulatory recommendations. Buffery PJ, Strother RM. N Z Med J. 2015 Jun 12;128(1416):66-74. Review.
antiemetics• antihistamine
–diphenhydramine (benadryl) •oral or rectal
• phenothiazines –compazine
• IV or rectal • HT3 Antagonists
–Ondansetron (Zofan), granisitron (Kytril) no advantage over conventional agents
–need EKG for ondansetron, QT issues
botox & ACG 2013 gastroparesis guidelines
“intrapyloric injection of botulinum toxin is not recommended for patients with gastroparesis based on randomized controlled trials”
(Strong recommendation, high level of evidence)
botox & saline, same outcomeAliment Pharmacol Ther. 2007 Nov 1;26(9):1251-8. Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Arts J, Holvoet L, Caenepeel P, et al.
METHODS: Twenty-three gastroparesis patients (five men, age 45 +/- 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 x 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student's t-test. RESULTS: Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t(1/2) (3.4 +/- 7.4 vs. 16.3 +/- 8.3, N.S.) and liquid t(1/2) (8.2 +/- 13.7 vs. 22.5 +/- 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 +/- 1.5 vs. 3.8 +/- 1.5, N.S.). CONCLUSION: In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.
abstract #467 ACG 2011: botox &/or pyloric balloon with normal 3 cpm EGG
• 18 patients with normal EGG, slow GES, normal EGD
• 4 quadrant botox 100 mcg or 20 mm balloon x 2 minutes
• If no symptom improvement, other intervention done
• 15 improved after 2 interventions, 3 no response
• symptom free for 4 months average
• retreatment at relapse
botox- what to do?World J Gastrointest Endosc. 2015 Jul 10;7(8):790-8. doi: 10.4253/wjge.v7.i8.790. Endoscopic botox injections in therapy of refractory gastroparesis. Ukleja A, Tandon K, Shah K et al.
All the open label trials have reported the intrapyloric BT-A injection to be useful therapy in GP. However, two small prospective randomized control trials (RCT) did not show positive response to botox injection in regards to symptomatic improvement and rate of gastric emptying. Both studies in different subgroups (DGP vs IGP) of patients have not proven BT-A to be superior to normal saline injection
Twenty-five patients (19 females; 6 males) were included in the analysis. The causes of GP were idiopathic 17, diabetes 6, and postsurgical 2. Mean follow up was 31 mo. Seventy-two percent of our patients noticed significant (> 50%) symptom improvement. The patients who benefited the most from BT-A injection were males and those with IGP. Twenty-eight percent of patients (7/25), non-responders to botox therapy underwent laparoscopic GES placement. Reduction in number of ER visits and hospitalizations was reported by 24% of patients.
Botox injections should not be used routinely in all GP cases.
gastric electrical stimulation• size of a cardiac pacemaker • implanted subcutaneously in the abdominal wall at the time of laparoscopy or laparotomy when electrodes are placed in the smooth muscle about 9.5-10 cm from the pylorus along the greater curvature of the antrum
• 2 electrodes are placed 1 cm apart, tangentially, deep in the muscularis propria
• delivers electrical stimuli to the stomach wall with a higher frequency (12 cpm) than the intrinsic gastric slow wave (2.5-3.5 cpm), but uses low-energy levels (300 microsec pulse width and 4-5 mA)
• most common complication is pacemaker hardware infection requiring device removal, approximately 5% of patients, most with diabetes
WAVESS (Worldwide Anti-Vomiting Electrical Stimulation Study)
50% of patients normalized their gastric emptying times at 12 months
no association between this observation and symptomatic improvement
symptomatic improvement that has been observed is caused by modulation of enteric or afferent neural activity that influences symptom perception or that influences a central nausea and vomiting control mechanism
GES therapy changes fundic relaxation, the autonomic nervous system, and gastrointestinal hormone levels. Abell TR, McCallum RW, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. 2003;125:421-428.
gastric electrical stimulation• severe nausea and vomiting
(occurring on average at least once daily) refractory to aggressive antiemetic and prokinetic drug therapy for at least one year in duration
• Enterra Therapy system has been approved as a humanitarian exemption device only for diabetic and idiopathic gastroparesis
• symptom severity and gastric emptying improves with DG, but not with IG or PSG
causal understanding due to ges• one third of patients with idiopathic and diabetic gastroparesis
• absent cells of Cajal on full-thickness gastric biopsies • the pacemaker cells in the gi tract
• increased abnormalities of gastric slow waves • more severe symptom status • poorer outcome with GES therapy
Interstitial Cells: Regulators of Smooth Muscle Function. Kenton M. Sanders, Sean M. Ward,et al. Physiological Reviews Published 1 July 2014 Vol. 94 no. 3, 859-907
acupuncture “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) (ACG 2013 guidelines)
acupuncture & diabetic gastroparesisAcupunct Med. 2015 Jun;33(3):204-9. doi: 10.1136/acupmed-2014-010670. Epub 2015
Feb 17.The short-term effects of acupuncture on patients with diabetic gastroparesis: a randomized crossover study. Li G, Huang C, Zhang X et al
METHODS: In a single-blind controlled crossover trial, 25 patients with diabetic gastroparesis were randomly assigned to undergo 1 week of real acupuncture (RA) treatment followed by 1 week of sham acupuncture (SA) treatment, or vice versa, with a washout of 1 month in between. Before and after each intervention, gastric retention, the Gastroparesis Cardinal Symptom Index (GCSI), fasting blood glucose (FBG) and HbA1c levels were measured. RESULTS: 21 patients completed the study. Compared with SA treatment, RA treatment was associated with significantly greater reductions in gastric retention at 2 h (-11.1±7.0%; 95% CI -13.6% to -6.2%; p<0.01) and at 4 h (-5.0±2.8%; 95% CI -6.0% to -0.2%; p=0.04) and in GCSI score (-8.0±3.4; 95% CI -8.4 to -2.8; p<0.01). There were no significant differences in FBG and HbA1c levels between RA and SA treatments. CONCLUSIONS: In patients with diabetic gastroparesis, 1 week of short-term manual acupuncture reduces gastric retention and improves gastroparesis symptoms.
Zusanli (ST 36) & Weishu (BL 21)
acupoint injectionZhen Ci Yan Jiu. 2014 Oct;39(5):406-9. Observation on therapeutic effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome. Zhang CN, Huang XK, Luo Y, et al. OBJECTIVE: To observe the clinical effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome (PGS). METHODS: A total of 46 patients with PGS(from abdominal surgery) were randomly divided into control and acupoint injection groups (n=23 in each group). Patients of the acupoint injection group were treated by injection of Metoclopramide (5 mg+ normal saline) into bilateral Zusanli (ST 36) and Weishu (BL 21) alternatively, while patients of the control group treated by injection of 10 mg of Metoclopramide into the deltoid muscle and gluteus maximus muscle alternatively. The treatment of both groups was conducted once daily for 14 days. A 3-point scale of clinical symptoms (abdominal distension, belching, nausea-vomiting, upper-abdominal distending pain, sour regurgitation and gastric burning sensation) was used to evaluate the therapeutic effect. RESULTS: There were no statistical differences between two groups in clinical symptom scores before the treatment (P>0.05). Following treatment, the clinical symptom scores of both groups were significantly decreased in comparison with pre-treatment (P<0.05) and the scores of the acupoint injection group were significantly lower than those of the control group (P<0.05). Of the 23 PGS patients in the control group and acupoint injection group, 0 and 2 were cured, 5 and 10 were significantly improved, 10 and 9 were improved, 8 and 2 failed, with the effective rates being 65.22% and 91.30%, respectively. CONCLUSION: Acupoint injection of Metoclopramide is effective for improving clinical symptoms of PGS patients.
control group n=22
acupoint injection group n=24
‘cured' 0 2
significant improvement
5 10
improved 9 10
failed 8 2
effective rates 65.22% 91.30%
sometimes nothing works
jejenostomy tube or decompressive PEG
• Rarely needed
All about that pace video
