Upper GI Bleeds Does the data support our practice?

Upper GI Bleeds Does the data support our practice? William J Roper

Studies • Daneshmend et al. Omeprazole vs placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. BMJ 1992 Jan 18;304(6820):143-7. • Kaviani et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: a prospective, double-blind, randomized clinical trial. Aliment Pharmacol Ther 2003; 17: 211-216. • Baradarian et al. Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol 2004; 99:619.

Study Design • Prospective, double blind, randomized, placebo controlled, intent to treat. • Omeprazole 80mg IV, then 40mg IV TID x3, then 40mg PO BID. • 1147 patients (569 placebo 578 treated) • Outcomes: all cause mortality, rate of rebleed, transfusion requirement, (and effect of treatment on 1o endoscopy). Daneshmend et al. Omeprazole vs placebo for acute upper gastrointestinal bleeding: BMJ 1992

Criteria • Inclusion criteria: all patients with overt UGIB, hematemesis or melena <24 hrs. • Exclusion criteria: age < 18, pregnant, severe illness (terminal or advanced malignancy), bleeding requiring immediate surgery, trivial bleed, bleeding during previous admission, prior participation in this study or inability to start treatment in <12 hours, or contraindication to medications (warfarin, phenytoin) Daneshmend et al. Omeprazole vs placebo for acute upper gastrointestinal bleeding: BMJ 1992

Results • Death: Tx: 6.9% Placebo: 5.3% (ns) • Transfusion: Tx: 53% Placebo: 52% (ns) • Rebleed: Tx: 18% Placebo: 15% (ns) • Bleed Stigmata: Tx: 33% Placebo: 45% (p<0.0001) • Blood in stomach, red clot on lesion, active bleed, black spot on lesion, visible vessel • “Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis or melaena.” Daneshmend et al. Omeprazole vs placebo for acute upper gastrointestinal bleeding: BMJ 1992

Cochrane Collaboration • Dorward et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding (review). The Cochrane Library 2007, Issue 1 • No difference in mortality, rebleed, or surgery. • Non-robust reduction of stigmata of recent hemorrhage. • Reduction in stigmata may reduce rate of endoscopic intervention, and thus be cost effective.

IV vs PO PPIs? • IV is quicker in onset, and more expensive than PO. • There are currently no trials of IV vs PO published • Is PO effective?

Study design • Prospective, double blind, randomized, placebo controlled trial. • 149 patients (treatment:71, placebo:78) • Omeprazole PO 20mg Q 6 hours Kaviani et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: 2003;

Criteria • Inclusion criteria: UGIB with active bleeding ulcer on EGD. • Exclusion criteria: age<15, low risk bleeds, uncertain or unknown bleed sites, patients on H2RA or PPI, probable gastric malignancy, or failure of endoscopic treatment. Kaviani et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: 2003;

Results • Death: Tx: 0% Placebo: 1% (ns) • Rebleed: Tx: 12% Placebo: 26% (0.022) • Transfuse: Tx: 40% Placebo: 72% (0.049) • Hospital >5d: Tx: 1% Placebo: 8% (0.034) • Unable to compare to IV trials due to different patient populations Kaviani et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: 2003;

What about early resuscitation? • Risk factors for bad outcomes are: • Advanced age • Co-morbid conditions • Hemodynamic compromise (Rockall et all. Incidence & mortality from acute upper gastrointestinal hemorrhage in the UK. Br Med J 1995; 311: 222-6) Baradarian et al. Early intensive resuscitation of patients with UGIB decreases mortality. 2004.

Study Design • Consecutive cohort • 72 patients (36 standard, 36 intensive) • Observe & collect data for first 4 months • Then early and intensive resuscitation for 4 months Baradarian et al. Early intensive resuscitation of patients with UGIB decreases mortality. 2004.

Criteria • Inclusion: • melena, hematemesis, or massive hematochezia • positive NG aspirate for blood • HR > 100 or SBP <100 • No exclusion criteria Baradarian et al. Early intensive resuscitation of patients with UGIB decreases mortality. 2004.

Methods • Timed correction of instability: • HR < 100 for > 10 minutes • SBP > 100 for > 10 minutes • HCT > 28% • INR < 1.8 • Additional physician to follow UGIB. Baradarian et al. Early intensive resuscitation of patients with UGIB decreases mortality. 2004.

Results Baradarian et al. Early intensive resuscitation of patients with UGIB decreases mortality. 2004.

In Practice • Prior to EGD, PPIs do not reduce mortality, rebleeds or surgery, (might make our GI colleagues job easier) • PO PPIs are effective in bleeding ulcers (but only after receiving an EGD) • No data for PO vs IV • Early intervention in UGIB is a Good Thing™

Upper GI Bleeds Does the data support our practice?