Summary

ACG 2021 guideline on management of overt upper GI bleeding, focused on initial resuscitation, risk stratification, pre-endoscopic management, endoscopic hemostasis for ulcer bleeding, and post-endoscopic antisecretory therapy. Updates from the 2012 guideline include expanded discharge criteria (GBS ≤1 instead of 0), inclusion of intermittent high-dose PPI regimens, new endoscopic modalities (TC-325, over-the-scope clips, APC, soft monopolar electrocoagulation), addition of twice-daily oral PPI through day 14 in high-risk patients, and a preference for transcatheter arterial embolization over surgery when endoscopy fails.

Key Recommendations

Discharge from the ED with outpatient follow-up if Glasgow-Blatchford score is 0–1 and no other reason for admission.
Use a restrictive RBC transfusion threshold of hemoglobin <7 g/dL in hemodynamically stable hospitalized patients; consider 8 g/dL for pre-existing cardiovascular disease and transfuse earlier in hypotensive or exsanguinating patients.
Give a pre-endoscopic erythromycin IV infusion to improve visualization and reduce repeat endoscopy and length of stay.
Do not routinely recommend for or against pre-endoscopic PPI; may be used if endoscopy is delayed or unavailable.
Perform upper endoscopy within 24 hours of presentation for hospitalized patients with UGIB; do not pursue endoscopy <12 hours in high-risk patients as it has not shown benefit and may harm if resuscitation is incomplete.
Apply endoscopic hemostatic therapy to ulcers with active spurting/oozing bleeding and nonbleeding visible vessels; endoscopic therapy for adherent clots is optional.
First-line endoscopic modalities with strongest evidence: bipolar electrocoagulation, heater probe, or absolute ethanol injection; clips, APC, soft monopolar electrocoagulation, and TC-325 are acceptable alternatives.
Do not use epinephrine injection as monotherapy; always combine with a second hemostatic modality.
Use TC-325 hemostatic powder spray for actively bleeding ulcers (not nonbleeding lesions); reserve over-the-scope clips for recurrent bleeding after prior successful hemostasis.
After successful endoscopic hemostasis, give high-dose PPI (continuous or intermittent) for 3 days, then twice-daily oral PPI through 2 weeks post-endoscopy in high-risk patients.
For recurrent ulcer bleeding after endoscopic hemostasis, repeat endoscopy rather than surgery or TAE.
If endoscopic therapy fails, use transcatheter arterial embolization rather than surgery.

Thresholds & Doses

Glasgow-Blatchford score 0–1: criterion for ED discharge with outpatient management (~1% risk of intervention/death).
RBC transfusion threshold: hemoglobin <7 g/dL (general); <8 g/dL with pre-existing cardiovascular disease.
Erythromycin: 250 mg IV infused over 5–30 minutes, given 20–90 minutes before endoscopy.
Endoscopy timing: within 24 hours of presentation for admitted UGIB patients.
Continuous high-dose PPI post-hemostasis: 80 mg IV bolus followed by 8 mg/hr infusion for 72 hours (3 days).
Intermittent high-dose PPI post-hemostasis: 40 mg PO/IV 2–4 times daily for 3 days, with optional 80 mg initial bolus (total ≥80 mg/day).
After initial 3-day high-dose PPI: twice-daily oral PPI (e.g., esomeprazole 40 mg BID) through day 14 in high-risk patients, then once-daily.
Bipolar electrocoagulation: 3.2-mm large probe, ~15 W with firm pressure, 8–10 second applications.
Heater probe: 30 J applications.
Absolute ethanol injection: 0.1–0.2 mL aliquots, total volume capped at 1–2 mL.
Epinephrine: 1:10,000 dilution in 0.5–2.0 mL aliquots (always combined with second modality).
Argon plasma coagulation: gas flow 1–2 L/min, power 40–70 W, probe 2–10 mm from mucosa.
Soft monopolar electrocoagulation: soft coagulation mode, 50–80 W, 1–2 second applications, max voltage 200 V.

Citations

Risk stratification section / Table 2 — Glasgow-Blatchford score 0–1 supports ED discharge.
Red blood cell transfusion section / Table 3 — restrictive transfusion threshold of 7 g/dL based on Villanueva RCT.
Pre-endoscopic medical therapy / Table 4 — erythromycin 250 mg IV pre-endoscopy reduces repeat endoscopy and length of stay.
Timing of endoscopy section / Table 6 — endoscopy within 24 hours; urgent <6h not superior in high-risk patients (Lau 2020).
Choice of endoscopic hemostatic therapy / Table 7 — meta-analytic efficacy of bipolar/heater probe, ethanol, clips, APC, soft monopolar.
Figure 3 — endoscopic and medical therapy algorithm by ulcer stigmata.
Antisecretory therapy after endoscopic hemostatic therapy — high-dose PPI (80 mg bolus + 8 mg/hr × 72h) and intermittent regimens.
Recurrent ulcer bleeding section / Table 8 — repeat endoscopy preferred over surgery (Lau 1999 RCT).
Failure of endoscopic therapy section — TAE preferred over surgery (Tarasconi meta-analysis; Sverden cohort).