UPPER GI BLEEDING:

GUIDELINES AND BEYOND

DISCLOSURES

• Data safety monitoring boards

– Bayer

• Medications for non-approved indications

– PPIs, erythromycin, octreotide, antibiotics for

UGI bleeding

UGIB: GUIDELINES AND BEYOND Outline

• Initial assessment and treatment of patients

with UGI bleeding

• Management of bleeding ulcers

• Management of bleeding varices

ASSESS RISK OF

PATIENT WITH UGIB

PRE-ENDOSCOPIC RISK SCORES

• HR, systolic BP

• Age

• Comorbidities

• BUN

• Hemoglobin

• Systolic BP

• Pulse

• Melena

• Syncope

• Hepatic disease

• Cardiac failure

Rockall (0-7) Blatchford (0-23) AIMS65 (0-5)

Rockall et al. Gut 1996;38:316; Blatchford et al. Lancet 2000;356:1318; Saltzman et al. GIE 2013;77:551

Endoscopic therapy,

surgery, transfusion, death

Death; further bleeding

• Albumin

• INR

• Altered mental

status

• Systolic BP

• Age

Death

PRE-ENDOSCOPIC UGIB SCORING SYSTEMS Prospective Assessment--6 Centers (US, Europe, Asia, NZ; N=3171)

Area Under Receiver Operating Characteristic (AUROC) Curve

Death Rebleed Intervention

or Death

Hospital

stay >3d

Blatchford 0.70 0.71 0.89 <0.70

Rockall 0.76 0.62 0.69 <0.70

AIMS65 0.79 0.62 0.70 <0.70

Laursen et al. UEGW 2015

0.9-1.0: Excellent

0.8-0.9: Good

0.7-0.8: Fair

PRE-ENDOSCOPIC RISK ASSESSMENT

• Stratify patients into high/low risk categories

– Level of care (ICU, ward, discharge)

– ?Timing of EGD

• Limitation for individual patient

– Can’t define risk with very high confidence

• Blatchford score 0 of 23: < 1% have intervention

– ? discharge from ED without endoscopy

Rockall et al. Gut 1996;38:316; Blatchford et al. Lancet 2000;356:1318; Stanley et al. Lancet 2009;373:42;

Pang et al. GIE 2010;71:1134; Chen et al. Am J Emerg Med 2007;25:774; Laine, Jensen AJG 2012:107:345

MEDICAL THERAPY

BEFORE ENDOSCOPY?

PRE-ENDOSCOPIC MEDICAL THERAPY

• PPI

– Fewer high-risk stigmata; no change in clinical outcomes

• If endoscopic therapy not available, less ulcer rebleeding

• Erythromycin

– 1st EGD diagnoses, transfusions; bleeding not shown

• Cirrhotic patients

– Vasoactive drug (e.g., octreotide)

• Better 12-hr bleeding control

– Antibiotics

• Significantly reduced infections, rebleeding, mortality

APT 2011;34:166; Gastro 2002;123:17; AJG 2006;101:1211; GIE 2002;56:174; NEJM 2007;356:1631; Mayo Clin Proc 2007;82:286; Lancet

1995;346:865; Lancet 1997;350:1495; Cochrane 2010 Issue 9. Art. No.: CD002907

TIMING OF ENDOSCOPY

TIMING OF ENDOSCOPY FOR UGIB

• Patients hospitalized with UGIB

– ≤ 24 hrs • length of stay, surgery

• Low-risk patients (normal VS, no comorbidity)

– As soon as possible in non-emergent setting

• ≤ 2-6 hrs lowers cost by allowing early discharge (~40-45%)

• High-risk patients (e.g., BP, HR, cirrhosis)

– Consider ≤ 12 hrs • May transfusions, hospital days, mortality

– ?Avoid <2 - <6 hrs

• May adverse events, mortality

Cooper et al. Med Care 1998;36:462; GIE 1999:49:145; Lee et al. GIE 1999;50:755; Bjorkman et al. GIE 2004;60:1; Lin et al. JCG 1996;22:267;

Lim et al. Endoscopy 2011; 43:300; Tsoi et al. Nat Rev Gastr Hep 2009;6:463; Yen et al Am J Em Med 1997;15:644; Laursen et al UEGW 2015

MANAGEMENT OF

BLEEDING ULCERS

STIGMATA OF HEMORRHAGE

• Stigmata prognostic, dictate management

• Further bleeding risk (descending order)

– Active spurting

– Non-bleeding visible vessel

– Active oozing

– Adherent clot

– Flat pigmented spot

– Clean base

Laine, Jensen. AJG 2012;107:345

Endoscopic therapy; Intensive PPI

± Endoscopic therapy; Intensive PPI

No endoscopic therapy; Standard PPI

ENDOSCOPIC THERAPY Dual Therapy vs. Monotherapy

• Epinephrine should not be used alone

– Less effective than other monotherapies

– Significant benefit by adding 2nd modality

• Thermal, sclerosant, clips can be used alone

• Sclerosant, clips alone may be less effective

for initial hemostasis in active bleeding

Laine, McQuaid. GIE 2009;7:33; Barkun et al. AIM 2010;152:101; Laine, Jensen AJG 2012;107:345

TECHNIQUES FOR ENDOSCOPIC THERAPY Thermal Therapy

• Large 3.2 mm probe with the least angulation and

as close as possible with firm/maximal pressure

• Multiple applications in ulcer base around and on

the bleeding site until bleeding stops, vessel

flattens, and base whitens

• Bipolar electrocoagulation (BPEC): 8-10 second

applications at setting ~15W

• Heater probe: setting of 30 joules

Laine. Gastro 1991;100:107; Laine, Jensen . AJG 2012;107:345

TECHNIQUES FOR ENDOSCOPIC THERAPY Injection Therapy

• Epinephrine (1:10,000 or 1:20,000)

– 0.5 – 2.0 ml aliquots around and in bleeding site

– Active bleeding: treat until bleeding stops, slows

– Non-bleeding: all 4 quadrants around bleeding site

• Absolute alcohol

– 0.1 – 0.2 ml aliquots with limitation of 1 – 2 ml

• Concern about tissue injury with higher volumes

Laine, Jensen . AJG 2012;107:345

TECHNIQUES FOR ENDOSCOPIC THERAPY Clips

• Place clips over the bleeding site and adjacent to

the stigmata of hemorrhage

– Attempting to close the underlying artery

Laine, Jensen . AJG 2012;107:345

ANTISECRETORY THERAPY

• Active bleeding, visible vessel, clot

– IV PPI bolus followed by continuous infusion for

3 days recommended by current guidelines

– Intermittent PPI (oral or IV) comparable to 3-day

course of continuous infusion

– Twice-daily oral PPI from day 4 to 14

• Flat spot, clean base

– Standard oral PPI

Laine, McQuaid CGH 2009;7:33; Barkun et al. AIM 2010;152:101; Laine, Jensen AJG 2012:107:345;

Sachar et al. JAMA Int Med 2014; Cheng et al. Gut 2014;63:1864

MANAGEMENT OF

VARICEAL BLEEDING

COAGULOPATHY AND

THROMBOCYTOPENIA

PT IS NOT A RELIABLE INDICATOR OF COAGULATION STATUS IN CIRRHOSIS

• PT measures procoagulant activity only

• Parallel in pro- and anti-coagulant factors

– Thrombin generation: cirrhotics ≈ healthy subjects

• Elevated PT or INR not predictive of peri-

procedural bleeding in SR of 25 studies

Tripodi et al. NEJM 2011;365:147; Segal et al. Transfusion 2005;45:1413; Tripodi et al. APT 2007;26:14

FRESH FROZEN PLASMA

FOR PROLONGED

PROTHROMBIN TIME

THROMBOCYTOPENIA Platelet Transfusion for Bleeding or High-Risk Procedures?

• Platelets from cirrhotic patients generate

thrombin ~normally

• Decreased platelets → ↓thrombin generation

– 56,000/mm3 generates thrombin at the 10th

percentile of control values

– Rationale for platelet transfusion in patients with

bleeding or undergoing surgery

Tripodi et al. Hepatology 2006;44:440

MANAGEMENT OF ACUTE

BLEEDING EPISODE

MANAGEMENT OF ACUTE

ESOPHAGEAL VARICEAL BLEEDING

• Ligation + vasoactive medication (octreotide)

– Ligation superior to vasoactive medication

– Ligation + octreotide superior to ligation alone

• Consider early TIPS in high-risk patients

– Child C (score ≤ 13), or Child B with active bleeding

• Significant decreases in further bleeding and mortality

– Non-significant decreases in encephalopathy

• Covered SEMS an option if refractory

de Franchis J Hepatol 2015;63:743; Chen et al. J Chinese Med Ass 2006;69:60; Sung et al. Lancet 1995;346:1666;

Monescillo et al. Hepatol 2004;40:793; Garcia-Pagan, et al. NEJM 2010;362:2370

PREVENTION OF RECURRENT

VARICEAL BLEEDING

PREVENTION OF RECURRENT

ESOPHAGEAL VARICEAL BLEEDING

• Ligation + β-blocker

– Combination more effective in reducing variceal

rebleeding than either therapy alone

de Franchis J Hepatol 2015;63:743; Thiele et al. APT 2012;35:1155

PREVENTION OF RECURRENT

ESOPHAGEAL VARICEAL BLEEDING Other Medical Therapies?

• Nitrate (ISMN) + β-blocker decreases HVPG,

variceal rebleeding vs. β-blocker alone

– Increased side effects

• Carvedilol decreases HVPG more frequently

than β-blocker and is clinically effective

– Not different than ISMN + β-blocker or ligation in

RCTs

Gluud et al. APT 2010;32:859; Lo et al. J Gastro Hep 2012;27:1681; Stanley et al. J Hepatol 2014;61:1014

RECURRENT VARICEAL BLEEDING

DESPITE 2° PREVENTIVE THERAPY

• TIPS

de Franchis J Hepatol 2015;63:743

RECURRENT VARICEAL BLEEDING

DESPITE 2° PREVENTIVE THERAPY

• TIPS

– ?May consider surgical decompression if

well-compensated liver disease

– ?May consider BRTO* if TIPS high-risk/difficult

• Portal vein thrombosis, high MELD, encephalopathy

• Via shunt from renal vein to portal system

de Franchis J Hepatol 2015;63:743; Garcia-Tsao et al. Hepatology

2008;47:1764; Henderson et al. Gastro 2006;130:1643; Dadabhai et al.

Hepatology 2012;55:1301-4

* balloon-occluded retrograde transvenous obliteration

INITIAL MANAGEMENT OF UPPER GI BLEEDING

• Assess risk

• Pre-EGD medications

– Consider erythromycin, PPI

• PPIs recommended if EGD delayed or not done

– Cirrhotic: octreotide (w/o PPI), antibiotic

• Early EGD (< 24 hrs)

– Low-risk: as early as 2-6 hrs lowers costs

– High-risk: < 12 hrs may improve outcomes

MANAGEMENT OF MAJOR ULCER BLEEDING

• Endoscopic therapy (repeat for rebleed)

• Constant infusion IV PPI vs. intermittent PPI

• Treat patients with

– Active bleeding

– Non-bleeding visible vessel

– Adherent clot (? PPI alone)

MANAGEMENT OF

ESOPHAGEAL VARICEAL BLEEDING

• Acute Bleeding Episode

– Vasoactive drug (e.g., octreotide x 2-5 days)*

– Antibiotics*

– Endoscopic ligation

– Consider TIPS in high-risk patients

• Prevention of Recurrent Bleeding

– Endoscopic ligation

– β-blocker

• TIPS if failure of medical/endoscopic therapy

* Begin before EGD