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Home , Gastric lavage, Hematochezia

Gastrointestinal : Upper, Lower and Everything Between Matthew C. Rice, MD Ochsner Health System Department of Medicine Section of & Disclosures

• I have no relevant conflicts of interest GI bleeding: Definitions

• Upper GI – bleeding proximal to Ligament of Treitz • Lower GI – bleeding distal to the Ligament of Treitz • For purposes of management – area from cecum to • Middle GI – small bowel • Area between ampulla of Vater and the ileocecal valve Gunjan, Deepak et al. “Small bowel bleeding: a comprehensive review.” Gastroenterology report vol. 2,4 (2014): 262-75. doi:10.1093/gastro/gou025 • Distinct from colonic bleeding (presentation, management, and outcomes)

Prakash C , Zuckerman GR . Acute small bowel bleeding: a distinct entity with significantly different economic implications compared with GI bleeding from other locations . Gastrointest Endosc 2003 ; 58 : 330 – 5 • Presumed small bowel bleeding when no source found during routine upper and lower GI Bleeding: Definitions

Overt GI bleeding manifest as visible red blood or altered blood in emesis or feces Occult IDA and/or positive FOBT; no visible blood in feces Obscure Recurrent or persistent overt or occult GI bleeding without bleeding source at initial endoscopy/evaluation

IDA : iron deficiency anemia FOBT: test

From Zuckerman, Lewis, et al. (AGA Clin Practice Committee). Gastroenterol 2000; 118: 201 From Zuckerman, Lewis, et al. (AGA Clin Practice Committee). Gastroenterol 2000; 118: 201 Epidemiology of overt bleeding

Upper GI Lower GI Middle GI (small bowel) • ~70% of GI bleeding cases • ~20% of all GI bleeding • ~5-10% of all GI bleeding cases • ~100 cases hospitalizations/100,000 • ~21 hospitalizations / • M>F persons per year 100,000 persons per • Increases with age • M>F year • Increases with age • M > F • Mortality 10% Rockall, BMJ 1995, 311: 222 • More marked increase • Longer hospital stays, higher • Mortality 7-14% with age cost, higher number of rd Rockall, BMJ 1995; 311: 222 • 3 decade: 1/100,000 diagnostic procedures and Longstreth, AJG 1995; 90: 206 • 9th decade: 200/100,000 blood transfusions Yavorski, AJG 1995; 90: 568. Prakash C et al. Gastrointest Endosc 2003 ; 58 : 330 – • Mortality 4% 5 Longstreth, AJG 1997; 92: 419 Manifestations

Hematemesis • Red blood or “coffee-ground” emesis

Melena • Black, “tarry”, foul-smelling • Blood in GI tract > 14 hours

Hematochezia • Bright red / maroon stool, bloody , clots • Usually LGI source : UGI source in 10-15% Laine L , Shah A . Randomized trial of urgent vs. elective in patients hospitalized with lower GI bleeding . Am J Gastroenterol 2010 ; 105 : 2636 – 41 How much blood loss produces…

Melena? 50-100cc

Hematochezia from 500-1000cc UGI source?

FOBT + ? From UGI source: 10-20 cc From LGI source: 0.5 cc Case 1

65-year old male presents to the ED with a 1-day history of melena and “coffee- What should be done ground” emesis. Pt reports feeling weak and light-headed. now? History • + NSAIDs QD x 1 month for back pain A)Emergent EGD in ER B)Admit to ward, EGD • EtOH: 1-2 glasses wine, 2-3 x week tomorrow • Hx of CAD- medically treated C)Start PPI (IV), no need for Physical exam EGD D)Fluid resuscitation, admit • VS: supine 120/70, 105-sitting 105/65, 120 to ICU, urgent EGD after • No PE signs of disease stabilization • Abd: soft, NT, rectal- black, tarry stool • N/G lavage: large vol clots, does not clear after 2L lavage Labs • CBC: wbc 9, hct 44, plts 180 • Coags: nl • Liver tests: nl Overt Upper GI Bleeding: Etiology

Causes of upper gastrointestinal bleeding • Peptic ulcer (31%-67%) • or (7%-31%) • Variceal bleeding (4%-20%) • Erosive (3%-12%) • Mallory-Weiss tear (4%-8%) • Tumors (2%-8%) • Aorto-enteric fistulas, arteriovenous malformations, or Dieulafoy’s lesions (2%-8%) Adapted from BMJ 2018;363:k4023 Initial assessment and risk stratification

• Hemodynamic status and resuscitation • Heart rate is more sensitive than blood pressure • 2 large-bore IVs • IV fluids – crystalloid • Blood transfusion target hemoglobin ≥7 g/dl • Data supports a restrictive transfusion policy • mortality (absolute risk reduction [ARR] 2.2 percent, relative risk [RR] 0.65, 95% CI 0.44- 0.97) and rebleeding (ARR 4.4 percent, RR 0.58, 0.40-0.84) Odutayo A et al. Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials. Lancet Gastroenterol Hepatol 2017; 2:354 • Higher targets for patients with intravascular volume depletion or other comorbid conditions (such as cardiovascular disease) ACG Practice Guidelines, AM J Gastroenterol 2012 Initial assessment and risk stratification • Glasgow-Blatchford Score (GBS)

BUN (mg/dL) 18.2-22.3

22.4-27.9

28-69.9

>70

BMJ 2018;363:k4023 Pre-endoscopic therapy

Prokinetic therapy • Decreases need for repeat endoscopy

• No effects on: • Number of units of blood transfusions • Length of hospital stay Effect of prokinetic on need for repeat endoscopy • Need for Gastrointestinal Endoscopy 2010 72, 1138-1145DOI: (10.1016/j.gie.2010.08.011) • Erythromycin (3 mg/kg IV over 20-30 min, at least 30 min prior to endoscopy) • Motilin receptor agonist • Promotes gastric emptying • Reglan • No significant benefits seen • Small sample sizes in studies Pre-endoscopic therapy RCT: IV PPI Infusion vs Placebo Before EGD • Endoscopic Tx of ulcers: – 22.5% (PPI) vs 36.8% (placebo) (p<0.05) • Hospitalized < 3 d – 61% PPI vs 49% placebo (P< 0.05) • No effect of PPI on: – Urgent endoscopy – Transfusions – Rebleeding – Death

• N = 638 UGIB: 377 PUD (60%) Lau J, 2007;356:1631. • Omeprazole 80 mg bolus, 8 mg/hr X 72 hr Pre-endoscopic therapy

PPI Therapy • No significant differences between continuous IV infusion vs intermittent IV dosing Sachar et al, JAMA Intern Med. 2014;174(11):1755 • PPI should be used if endoscopy will be delayed • Cochrane meta-analysis of RCTs of patients with UGI bleed who did not consistently receive endoscopic therapy • PPI associated with: • Reduced risk of rebleeding (OR=0.38, 0.18-0.81) • Reduced surgery (OR=0.62, 0.44-0.88; NNT=17) • No effect on mortality Leontiadis GI , Sharma VK , Howden CW. Mayo Clin Proc 2007; 82:286–96 Pre-endoscopic therapy

Gastric lavage (in upper GI bleeding) • Not required for diagnosis, prognosis, visualization, or therapeutic effect • Clear or bile stained aspirate seen in up to 18% of patients with upper GI source of bleeding • 15% of patient with active UGI bleed have clear/bile-stained aspirate Aljebreen AM , et al. Gastrointest Endosc 2004 ; 59 : 172 – 8 • Even in patients with signs of shock (BP<100, HR>100), only 60% had bloody aspirate Lin HJ , Kun W , Perng CL et al. J Clin Gastroenterol1996 ; 22 : 267 – 71 • Standard size NG tube are unlikely to clear clots Role for Endoscopy in UGI bleed

• Determine etiology of bleeding • Patient triage • Identify endoscopic signs as prognosticators for rebleeding, surgery, mortality • Endoscopic treatment of bleeding site Endoscopy - Timing

• “Early” EGD (within 24 hours) - now standard of care • RUGBE (Canada), AJG 2004: 76% w/in 24 hrs; median time: 12 hrs • Tsoi KKF , et al. Nat Rev Gastroenterol Hepatol 2009: Systematic review • Endoscopy within 12 h of presentation leads to increased use of endoscopic therapy for advanced stigmata of hemorrhage, which may not be necessary • No evidence exists for any clinical benefit of endoscopy performed within 12 h of presentation • Early endoscopy within 12 h of presentation does not reduce the rebleeding rate or improve survival of patients • Endoscopy within 24 h of presentation is recommended for management of upper gastrointestinal bleeding, because it has clinical benefits • Decreased length of stay and need for surgery • Endoscopy within 24 h of hospitalization aids risk assessment and reduces the length of hospital stay • Majority of patients do not require urgent nighttime EGD • Lau J, NEJM 2007;356:16 • N= 638 enrolled in RCT - PPI vs placebo prior to EGD next AM- 2 % required urgent night EGD • Risk of early endoscopy – potential for increased complications before appropriate resuscitation and stabilization • Risk stratification may have a role Endoscopy: Timing

• Low-risk • Hemodynamically stable, no serious comorbidities • Early endoscopy allows for earlier discharge • Lack of clinical benefit argues against “middle of the night” endoscopy • High-risk • Patient’s with hemodynamic instability (SBP < 100 mmHg, pulse > 100 bpm) and signs of active bleeding • Limited data available – possible improved clinical outcome from endoscopy within 12 hrs • Blatchford score ≥ 12 Lim LG , Ho KY , Chan YH et al. Endoscopy 2011;43:300–6 (observational study) • 44% higher mortality if endoscopy done >13 hrs after presentation • Presentation-to-endoscopy time – only variable significantly associated with mortality Endoscopy – Classification of Stigmata

Flat spot Clot

Clean base

From Laine, NEJM 1995; 331: 717.

Visible vessel Active bleeding Endoscopic signs as predictors of repeat bleeding, surgery, and mortality

From: Laine L, NEJM 1994; 331: 717. Endoscopic Therapy: Who to treat…

American Journal of Gastroenterology107(3):345-360, March 2012 Case 1: Upper Endoscopy Performed

Visible vessel in duodenal bulbar ulcer (3cm). Active bleeding started during EGD Successful hemostasis with contact prior to endoscopic therapy. thermocoagulation and hemoclips PPI use after endoscopic therapy

Meta-Analyses for PPI Therapy as an Adjunct After Endoscopic Hemostatic Therapy

Comparison End point Number of RR (95% CI) NNT (95% CI) comparisons Intravenous PPI: Further bleeding 4 0.40 (0.28–0.59) 12 (10–18) bolus plus continuos Surgery 3 0.43 (0.24–0.76) 28 (21–67) infusion v placebo Urgent intervention 3 0.31 (0.18–0.53) 8 (7–12) Mortality 4 0.41 (0.20–0.84) 45 (33–167)

Laine, L, Mcquaid, KR. Clin Gastroenterol Hepatol. 2009 Jan;7(1):33-47 PPI use after endoscopic therapy

Forest Plot of Studies Comparing Intermittent With Bolus Plus Continuous-Infusion Proton Pump Inhibitors in Patients With High-Risk Bleeding Ulcers The outcome examined was rebleeding within 7 days in the intention-to-treat population. Primary outcomes:

• Intermittent PPI therapy is noninferior to the currently recommended regimen of intravenous bolus plus continuous infusion of an intravenous PPI for 3 days.

• There is no increase in recurrent bleeding with intermittent vs continuous PPI therapy.

Sachar et al, JAMA Intern Med. 2014;174(11):1755 Hospitalization for NVUGI bleeding

• Most recurrent bleeding occurs within 3 days

Based on older studies, 1990’s ACG Practice Guidelines, AM J Gastroenterol 2012 • Recent RTC of high-risk ulcer treated with endoscopic therapy • 24% may rebleed beyond 3 days

• 6% of rebleeding occurs beyond 7 days Sung JJ , Barkun A , Kuipers EJ et al. Ann Intern Med 2009; 50:455–64 • Admit beyond 3 days not routinely recommended • Education regarding signs of recurrent bleeding Long-term prevention

Recommended management to prevent recurrent ulcer bleeding based on etiology of ulcer bleeding. CV, cardiovascular; H2RA, histamine-2 receptor antagonist; NSAID, non-steroidal anti- inflammatory drug; PPI, proton pump inhibitor. Management of Patients With Ulcer Bleeding

Laine, Loren; Jensen, Dennis M American Journal of Gastroenterology107(3):345-360, March 2012. doi: 10.1038/ajg.2011.480 Case 2

A 45 old female with known secondary to alcohol abuse presents with a 2- day history of melena. PE: Vitals: BP 85/65, HR 115 bmp Abd: soft, nontender, splenomegaly, shifting dullness Rectal: black, tarry stool N/G lavage: 200cc maroon blood / clots, clear after 1L lavage Labs: hct 27, plts 130, INR 1.7

She is presumptively dx’d in the ED with acute esophageal variceal hemorrhage, and is awaiting a bed in the ICU. Blood and FFP transfusions have been started. What should we do next? Antibiotics prophylaxis for cirrhotics with acute GI bleeding

RR with Abx 95% CI

Incidence of bacterial 0.40 0.32-0.51 infection mortality 0.73 0.55-0.95

Soares-Weiser, Cochrane Database Review, 2002 (CD002907) • 8 RCTs of Abx vs. placebo or no Abx: 864 pts • most treated with quinolones x 7days Control of Variceal Bleeding: non-endoscopic measures

Octreotide / somatostatin / vasopressin (or analogues) • Pharmaco-tx vs endo tx: • Pharmacotherapy + endo tx: Similar rates of initial hemostasis (80-84% vs 83-90%)

Similar rates rebleeding (14-25% vs 16-17%)

Planas, Hepatol 1994; 20: 370 Sung, Lancet 1993; 342: 637

Banares, Hepatol 2002 8 RCTs (1995-2001): 939 pts Case 2 : Endoscopy performed

Active variceal bleeding noted…

What types of endoscopic treatments are available ? Case 2 : Endoscopy performed

Endoscopic techniques for variceal hemorrhage Band ligation vs sclerotherapy • Similar initial hemostasis > 90% • Decreased complications • Esophageal strictures / ulcers From Rockey, NEJM 2001; 345:669 • Infections Lo, Hepatol 1997; 25:1101 Laine, Ann Int Med 1993; 119:1 Stiegmann, NEJM 1992; 326: 1527

• Decreased mortality From Helmy, APT 2001; 15: 575 19% vs. 35% Lo, Hepatol 1997; 25:1101 28% vs. 45% Stiegmann, NEJM 1992;326:1527 Case 2: Endoscopic therapy performed…

Deployment of bands was suboptimal due to ongoing hemorrhage and difficult visualization, and was unsuccessful. Sclerotherapy was also attempted, but failed.

What other treatment options are available ? Balloon Tamponade “ Minnesota Tube ” • High rates of initial bleed control (>70%) Fort, Hepatol 1990; 11:678 Paquet, Hepatol 1985; 5:580 • High rebleed rates (40%) Paquet, Hepatol 1985; 5:580 • Complications: esophageal perforation < 8% Chojkier, Dig Dis Sci 1980; 25:267 TIPS for Acute Refractory Variceal Hemorrhage

• ~ 10% fail endo tx Rockey, NEJM 2001; 345:669

• TIPS effective > 95% Sanyal, Gastroenterol 1996; 111:138 Boyer, Gastroenterol 2003; 124:1700 • Rebleed 18% • Mortality (in acute setting) 38% From Boyer, Gastroenterol 2003; 124:1700 Case 3

77 y/o man presents to ED with 1-day history of several episodes of large volume hematochezia. Initial BM had blood mixed with brown stool; subsequent BMs blood only. No prior GIB or endoscopic studies. Denies , vomiting, or .

PMH: 1. CAD – s/p stent placement 2004. Normal EF. 2. HTN 3. Osteoarthritis

Meds: aspirin, ibuprofen, simvastatin, beta-blocker Case 3

PE: Gen: awake, alert, cooperative. VS: P 85 BP 120/70 supine : P 87 BP 105/68 sitting Chest/CV: normal Abdomen: non-tender Digital exam: no prolapsed ; no palpable lesions; bright red blood on glove – with passage of further blood in ER.

Labs: Hct 35 (baseline 40) WBC 8,000; Platelets 200,000; INR 1.0

Nasogastric aspirate: no blood Case 3: What would you do?

• Observe. If no further bleeding, colonoscopy w/in 1-2 days; If continued bleeding, Tc-RBC scan +/- angiography

• Rapid bowel purge until clear then either urgent colonoscopy (if active or severe) or elective colonoscopy (if bleeding stops) Lower GI Bleeding

60-65% due to benign and readily treatable pathology Lower GI Bleeding: Characteristics

• Presents usually as maroon or red blood, may see clots • Rare cases of cecal/right colon sources presenting as tarry stools/melena • 15% of suspected lower GI sources are actually brisk upper GI • Usually stop spontaneously • Higher morbidity and mortality in older patients Lower GI Bleeding: Evaluation and Initial management • Focused history, physical and labs to determine severity, location and etiology • Symptoms and duration • Signs of hemodynamic instability • Labs: CBC, electrolytes, coagulation studies, type/crossmatch • Abdominal and vascular , radiation therapy, IBD, PUD, cardiopulmonary disease, renal disease, hepatic disease • Prior bleeding events • Medication use (NSAIDs, antiplatelet/anticoagulants) • Consider EGD in any patient with hemodynamic instability or risk factors and indicators of upper GI source • History of PUD, , and antiplatelet/anticoagulation use • BUN ratio >30:1 (likelihood ratio 7.5) • UGI source in 10-15% Laine L , Shah A . Am J Gastroenterol 2010 ; 105 : 2636 – 41 Evaluation and Initial management: Hemodynamic resuscitation • IV fluids to normalize blood pressure and heart rate prior to endoscopy • IV fluids should be given for hemodynamic instability • Controversy regarding timing, amount, and type of fluid • No clear benefit of colloid over crystalloid

Transfuse PRBC – Hb goal >7 g/dl Laine, Loren; Jensen, Dennis M. Amer J Gastro. 107(3):345-360, March 2012. • Transfusion strategies for LGI bleeding have not been established • Limited data available but findings are consistent with outcomes seen in blood transfusion strategies for UGI bleeding • Consider 9 g/dl in patients with massive bleeding or significant comorbidities (i.e. cardiovascular ischemia) Treatment: Controversy Treatment: Why the Controversy?

• Lack of definitions: hematochezia vs • Lack of sufficient training severe hematochezia • Rapid purge: what it means • Lack of good RCTs • How to look for bleeding source • Eminence-based vs evidence-based • How to treat • Lack of sufficient experience • Lack of positive reinforcement • Incidence UGIB > LGIB • “All I see is blood and tics” • VA: LGIB > UGIB • “I’ve never seen a bleeding site” • Old habits (and inertia) “Conventional” Approach to Lower GI Bleeding

Hematochezia

Admit, Resuscitate, Observe

Bleeding Stops Continued or Recurrent Bleeding Negative Elective Colonoscopy: Nuclear Bleeding Scan 24-48 hrs rebleed Positive Angiography Negative; stops bleeding Treatment: Early Colonoscopy

Strate L. Am J Gastro 2003: • N=252, LGIB Retrospective cohort: 1996-99 • N = 144 had inpatient colonoscopy (median time: 25 h) • Findings:

◼Earlier (<24 h) colonoscopy resulted in more definitive diagnoses and therapeutic intervention

◼Length of stay shorter w/ early colonoscopy • < 12 hours: 1.7 days (CI, 1.5-3.5) • 12-24 hrs: 2.1 days (CI, 1.9-3.1) • 24-48 hrs: 2.7 days (CI, 2.3-3.5) • > 48 hrs: 4.4 days (CI, 3.4-5.9)

◼In multivariate analysis, time to colonoscopy significantly associated with hospital LOS - HR: 2.02 (CI, 1.5-2.6) Treatment: Lead with your best option

• Colonoscopy is treatment of choice • 12-48 hrs of admission • Dx made in 74-90% • Rapid oral purge technique • Polyethylene glycol • 1 L every 30-45 min (consider N/G) • Median 5.5 L , 3-4 hrs Elta, GIE 2004; 59: 402 Treatment: Urgent colonoscopy

• Colonoscopy w/in 12-24 hours of admission • Rapid purge: Get serious! • PEG preps: 1 Liter q 30-45 minutes • Median 6 L (range: 4-14L) • Time required: 3-4 hrs • NG tube: required in one-third • Warning: risk of aspiration! • Consider: metoclopramide 10 mg IV • Goal: clear effluent (if not, give more) • Colonoscopy w/in 1 hr of clearance • If ongoing bleeding, colonoscopy when effluent is pink with no clots • Aspirate remaining gastric contents prior to sedation Treatment: Urgent vs “Conventional”

• Is one proven superior? No • Limited prospective comparisons • Variable patient selection • “severe” vs all-comers • Variable timing of colonoscopy • “Urgent” vs “early” • Type/quality of bowel prep • Rapid purge vs standard • Need well-designed, prospective RCT Treatment: How can clinical predictors help?

7 Factors identified with severe LGI • Stable VS, no recent BRBPR, no syncope bleeding: • Low risk of continued bleeding (no risk factors): <10% • Pulse ≥100 bpm • Systolic BP ≤115 mmHg • Standard bowel prep: non-emergent colonoscopy • >2 Comorbid illnesses • LIMITATION: This applies to small minority • Syncope • ≤4 hrs of • Risk of severe bleeding in everyone else is moderate to high evaluation • Moderate (1-3 risk factors): 43% • Aspirin use • • High (>3 risk factors): 79% Non-tender abdominal exam • So, initiate rapid purge on everyone with risk factors • Subsequent management determined by events over next few hours • No bleed: non-urgent evaluation • Continued bleed: urgent colonoscopy Strate L, et al: Am J Gastroenterol 2005;100:1821 prospective, observational cohort study 275 patients Case 3: urgent colonoscopy performed…

What is the diagnosis? Can this patient Treated with hemoclips be endoscopically treated? Treatment: Non-endoscopic options

Angiography / IR • Consider in patients with high-risk features and negative EGD who do not respond to resuscitation efforts (would not likely tolerate bowel preparation and colonoscopy) • +/- nuclear bleeding scan for localization • Requires 0.5-1.0 cc/min bleeding rate • Techniques: • intra-arterial vasopressin (>90% success, 50% rebleed) • Selective embolization (>90% success, 76% ITT basis) Complications: ischemia 7%, rebleed 20%, surgery 20% Gordon, Am J Surg 1997; 174. Surgery - measure of last resort for ongoing bleeding despite therapeutic interventions • Hemicolectomy with accurate localization (endo / IR) • Subtotal • Consider for large transfusion requirements: > 6U/24hrs Case 4

A 75-year old male with hx of HTN and osteoarthritis presents with 1-day history of hematochezia (large volume, maroon color). Denies nausea, vomiting, or abdominal pain.

PMH: otherwise unremarkable meds: ACE inhibitor, NSAIDs

PE: Patient is comfortable, no acute distress vitals- 130/90, 95 supine : 110/85, 98 sitting Abd- soft, nontender rectal- maroon stool, clots N/G lavage- bilious aspirate labs- plts 190, INR 1.1, init hct 32, 4hr f/u hct 30

Initial evaluation and treatment as per our algorithm. EGD and colonoscopy does not isolate a source What do we suspect? What are our options now? Small intestinal Causes of small bowel bleeding

bleeding: Etiology Source ACG Clinical Guideline: Diagnosis and Management of Small A cause identified in 75% of suspected Bowel Bleeding American Journal of cases Gastroenterology110( 9):1265-1287, September 2015. Small bowel angioectasia are the most common cause

Meta-analysis: Findings during DBE/VCE Vascular lesions: 24% Inflammatory: 16-18% Polyps/tumors: 11% Pasha, S. et al. Clinical Gastro Hep, 2008-06-01, Volume 6, Issue 6, Pages 671-676 Small intestinal bleeding

• As mentioned, only 5-10% of GI bleeding cases • Consider referral to tertiary center for evaluation • Usually requires specialized techniques and services for treatment • Wireless • Device-assisted deep • Interventional radiology Key Points:

• Most bleeding occurs from the UGI tract • PPI use for UGI bleeding has significant clinical benefits before and after endoscopy • Most recurrent bleeding from peptic ulcers occurs within the first 3 days • Octreotide decreases bleeding from and should be combined with endoscopic banding when possible • Most common causes of lower GI bleeding are treatable – colonoscopy is the test of choice • Small bowel bleeding is less common, usually treatable, and referral to a tertiary center may be needed Thank you!