OCTOBER 7-10 PHILADELPHIA, PENNSYLVANIA

Size: px

Start display at page:

Download "OCTOBER 7-10 PHILADELPHIA, PENNSYLVANIA"

Hollie Merritt
6 years ago
Views:

1 OMED 17 OCTOBER 7-10 PHILADELPHIA, PENNSYLVANIA 29.5 Category 1-A CME credits anticipated ACOFP / AOA s 122 nd Annual Osteopathic Medical Conference & Exposition Joint Session with ACOFP and Cleveland Clinic: Managing Chronic Disease Constipation and Opioid-Induced Constipation Scott Gabbard, MD The American College of Osteopathic Family Physicians is accredited by the American Osteopathic Association Council to sponsor continuing medical education for osteopathic physicians. The American College of Osteopathic Family Physicians designates the lectures and workshops for Category 1-A credits on an hour-for-hour basis, pending approval by the AOA CCME, ACOFP is not responsible for the content.

2 Constipation and OIC Scott Gabbard, M.D. Staff, Department of Gastroenterology Digestive Disease & Surgery Institute Assistant Professor of Medicine Lerner College of Medicine Cleveland Clinic Agenda Epidemiology Pathogenesis Diagnosis/testing Treatment OIC 1

3 Why is constipation important? How common is this? Prevalence: ~ 28%, Female predominance 8 million >$230 million Physician visits due to constipation each year in the US ( most nonspecialist) US annual direct medical costs Barucha AE et al. Gastroenterology 2013;144:

4 Excessive straining Hard stools What is constipation? Unproductive urge Infrequent stools Feeling of incomplete evacuation Heaton, Gut 1992;33:818 3

5 Why do patients get constipation? Constipation: Etiology Primary: - Normal transit (IBS-C) - Defecatory disorders (pelvic floor dysfunction) - Slow transit constipation (colonic inertia) Secondary: Drugs, Metabolic, Hormonal, Neurological, Obstructive, Malignant, rectocele Almost all studies on pathophysiology emanate from tertiary centers Barucha AE et al. Gastroenterology

6 Constipation: Primary Causes Retrospective review of >1000 patients with intractable constipation (by colonic transit and anorectal studies) - Slow transit constipation 11 percent - Dysynergic defecation 13 percent Combination of the two 5 percent - Irritable bowel syndrome/functional constipation 71 percent Nyam, Dis Colon Rectum 1997 Constipation Diagnostic testing Labs: - CBC, TSH, glucose, calcium, BMP Colonoscopy - >age 50 (if no previous screening) - Alarm symptoms (anemia, rectal bleeding, weight loss) - New onset disease 5

7 IBS - Definition Definition Rome IV - Recurrent abdominal pain (1 day/wk) in the previous 3 months, with a duration of at least 6 months Two or more: Related to defecation Change in frequency of stool Change in form of stool Prevalence = 12% Lacy et al. Gastroenterology, 2016 IBS-Subtypes Lacy et al. Gastroenterology,

IBS Treatment Step 1 Make a confident diagnosis!! - Use Rome IV criteria - Give the Rome IV papers to your patient (show diagnostic criteria) This is you!

8 IBS Treatment Step 1 Make a confident diagnosis!! - Use Rome IV criteria - Give the Rome IV papers to your patient (show diagnostic criteria) This is you! What not to do - We don t know what you have - It s probably just IBS, here s the door IBS Treatment Step 2 Patient: Why did I get IBS? - We think that many factors are at play Genetics Inflammatory/postinfectious event Sensitization of the visceral nerves Central sensitization - Show this figure to your patients (from NEJM 2017) Lacy et al. NEJM,

9 Step 3 - Reassurance Diagnosis 6 months 6 years after original diagnosis of IBS : Unchanged IBS symptoms:30 50% Symptom free: % Worsened IBS symptoms: 2 18% Alternative diagnosis: 2 5% Long term follow up 112 patients, mean FU 29 years Organic GI disease <10%, 15 yr. after diagnosis of IBS No impact on expected survival El-Serag HB, et al. Aliment Pharmacol Ther Owens DM et al. Ann Intern Med Step 4 - Fiber Dietary or commercial Start at 4-6 g/day and increase slowly to grams - Soluble fiber preferred (psyllium/ispaghula husk) 1 tsp = 4-6g of fiber - Prunes (6-12 BID) - Hemp seed extract (7.5g BID) Bloating/flatulence/abdominal distension main side effects Less effective in severe constipation and pelvic floor dyssynergia Bharucha et al. Gastroenterology 2013 Lacy et al. Gastroenterology,

10 Prunes 50g prunes (12 prunes) BID vs. 2 teaspoons of psyllium BID Significant increase in spontaneous BMs (SBM) from baseline in both groups Prunes resulted in significantly increased SBMs compared to psyllium No difference in adverse events Attaluri et al. APT 2011 Hemp Seed Extract Functional constipation 7.5 grams BID Responders - HS = 43.3% - Placebo 8.3% - NNT = 2.8 Adverse Events - Abdominal pain/bloating (13%; 3.4% for placebo) - Nausea (6.7% for HS and placebo) Cheng et al, AJG

11 Probiotics Certain strains may increase frequency, improve consistency - Bifidobacterium lactis DN Lactobacillus casei Shirota - Escherichia coli Nissle 1917 Lacy et al. Gastroenterology, 2016 Step 5 - Laxatives Poorly Absorbed Ions Magnesium: hypermagnesemia Phosphate: hyperphosphatemia Poorly Absorbed sugars Disaccharides (Lactulose): bloating Sorbitol: bloating Polyethylene glycol: Best data for osmotic laxatives Increases stool frequency Improves stool consistency Does not improve pain/bloating Barucha AE et al. Gastroenterology

Laxatives Stimulants Anthraquinones (senna): melanosis coli Ricinoleic acid (castor oil) : cramps Bisacodyl: Increases frequency, but SE of pain Emollients Mineral oil: fat malabsorption, anal

12 Laxatives Stimulants Anthraquinones (senna): melanosis coli Ricinoleic acid (castor oil) : cramps Bisacodyl: Increases frequency, but SE of pain Emollients Mineral oil: fat malabsorption, anal seepage Stool softeners (docusate): No data Lacy et al. Gastroenterology, 2016 Step 6 - Secretagogues Lubiprostone - Activates Chloride-2 channels - Enhances GI fluid secretion Phase III trials - Response rate = 17% vs. 10% for placebo NNT = 14 - SEs = Nausea (8%), diarrhea (6%) Dosing - IBS-C: 8mcg BID - CIC: 24mcg BID Drossman et al. APT

9% for placebo - NNT = 5 - Most common SE = diarrhea (19%) Dosing - IBS-C: 290mcg daily - CIC: 72mcg or 145mcg daily Chey et al, AJG.

13 Secretagogues - Linaclotide Linaclotide - GC-agonist, upregulates CFTR channels - Enhances GI fluid secretion Phase III data - Response rate 33.7% vs. 13.9% for placebo - NNT = 5 - Most common SE = diarrhea (19%) Dosing - IBS-C: 290mcg daily - CIC: 72mcg or 145mcg daily Chey et al, AJG Secretagogues - Plecanatide Plecanatide - GC-agonist Phase III data - Response rate 21% vs. 10% for placebo (durable CSBM) - 36% weekly responder vs. 16% with placebo - NNT AEs: Diarrhea (6%), sinusitis (2%) Dosing: 3mg daily (CIC) Miner et al. AJG

14 Step?? - Antidepressants SSRIs - Numerous serotonin receptors involved in IBS - Promote GI motility RCT fluoxetine 20mg daily - 85% symptom improvement (4.6 -> 0.7) vs. 35% with placebo (4.5 -> 2.9) Meta-analysis - NNT (SSRI) = 4 Cost!! Vahedi et al. APT What if my patient fails laxatives????? 13

15 Pelvic Floor Dysfunction Impaired rectal evacuation Prevalence = 26% Common symptoms - Difficult evacuation - Excessive straining - Manual disimpaction Physiology: - Contraction of anal sphincter during attempted defecation - Impaired evacuation (balloon, imaging) Kepenekci et al. Dis Colon Rectum Anorectal Physiology: Anorectal Angle Lembo A, et al. N Engl J Med. 2003;349:

16 Ano-rectal Manometry Detect features of dyssynergia Assess rectal sensation - Hypersensitivity = IBS Identify candidates for biofeedback Hirschsprung s disease Anorectal Manometry 15

Balloon expulsion Test not standardized 50-60 ml, water- filled

17 Balloon expulsion Test not standardized ml, water- filled balloon. Expulsion in <1 min An adjunct test for the diagnosis of dyssynergia Simulated Defecation mmhg Rectal Sensors Baseline sphincter pressure Sensor Position 10sec 16

18 Simulated Defecation mmhg Balloon 140 expulsion 120 Rectal Sensors Sensor Position 0 10sec 2 Simulated Defecation - Normal mmhg Sphincter relaxation 10sec Rectal Sensors Sensor Position 17

sec 2 Pelvic Floor Dysfunction - Treatment Biofeedback - Biweekly 1 hour sessions -

19 Dyssynergic Defecation mmhg 140 Balloon expulsion Simulated 120 Defecation Rectal Sensors No sphincter relaxation Sensor Position 0 10 sec 2 Pelvic Floor Dysfunction - Treatment Biofeedback - Biweekly 1 hour sessions - 86% of patients with improvement in symptoms Rao et al. Clin Gastroenterol Hepatol

dyssynergia Colon Transit - Radio-opaque Markers: Qualitative Single capsule, with 24 markers 1 capsule on

20 Slow Transit Constipation Colonic Inertia Symptoms of constipation (infrequent BM s, hard stool), absence of systemic disorders Most common in young women Reduction of colonic nerve fibers and ICC s May coexist with dyssynergia Colon Transit - Radio-opaque Markers: Qualitative Single capsule, with 24 markers 1 capsule on day 0 Abdominal x-ray day 5 (no laxatives) Normal = < 20% markers retained Hinton et al. Gut 1969;10:

21 Colonic Inertia - Treatment Laxatives Secretagogue - Linaclotide, lubiprostone, plecanatide Colectomy - Not for patients with Pelvic floor dysfunction Pain as predominant symptom Opiod-Induced Constipation Definition - A change from baseline bowel habits upon initiation of opioids that is characterized by any of the following symptoms: (1) reduced bowel movement (BM) frequency (2) development or worsening of straining to pass stool (3) a sense of incomplete rectal evacuation (4) harder stool consistency Up to 47% of patients on chronic opiates Highest prevalence in women and increasing age Argoff et al, Pain Med

consideration of prescription medication Argoff et al, Pain Med. 2015 Ueberall et al.

22 OIC - Diagnosis Bowel Function Index - Validated scale for assessing OIC - Mean of 3 variables - Change of >12 points is clinically significant - BFI > 30 should prompt consideration of prescription medication Argoff et al, Pain Med Ueberall et al. J Int Med Res OIC - Prevention Lifestyle changes - Fiber Laxatives - Senna - Docusate - PEG 21

23 OIC Lubiprostone Lubiprostone - 24mcg BID - NNT = ~12 - Adverse events (AEs) Diarrhea 11% Nausea 10% Vomiting 4% abdominal pain 7% Jamal MM, et al. AJG OIC - Methynaltrexone Methylnaltrexone - Peripherally-acting μ- opioid antagonist - SC: 8mg (up to 61kg); 12mg (>61kg) - Every 2-3 days - NNT = 3 - Adverse events Abdominal pain, nausea, vomiting similar to placebo Thomas J, et al. NEJM

OIC - Naloxegol Naloxegol - Peripheral opioid

events Diarrhea (3%) Abdominal pain (4%) Chey et

- 0.2mg PO daily - NNT = 5 - Adverse events

24 OIC - Naloxegol Naloxegol - Peripheral opioid antagonist - 25mg PO daily NNT = ~8 - Adverse events Diarrhea (3%) Abdominal pain (4%) Chey et al, NEJM OIC - Naldemedine Naldemedine - Peripherally acting muopioid receptor antagonist - 0.2mg PO daily - NNT = 5 - Adverse events Abdominal pain (6%) Diarrhea (7%) Nausea (5%) Hale et al. Lancet Gastroenterol Hepatol. 2017;2:

25 OIC - Alvimopan Peripherally acting μ-opioid antagonist FDA approved for post-surgical ileus - Short term use only Increased risk of myocardial infarction with use > 1 month - Not FDA approved for OIC!! Main Points - Constipation Diagnosis - Most often IBS/Functional Constipation Make a confident diagnosis! - Low threshold to refer patients to a center that performs anorectal manometry Treatment - Fiber Prunes or hemp seed extract may be preferred to psyllium - Laxatives - Secretagogues - Antidepressants - PT/Biofeedback 24

Elderly Man With Chronic Constipation

Elderly Man With Chronic Constipation Linda Nguyen, MD Director, Neurogastroenterology and Motility Clinical Assistant Professor Stanford University Overview Normal bowel function Defining Constipation: