EBQ:Transfusion strategies for acute upper gastrointestinal bleeding

Under Review Journal Club Article

Villanueva C. et al. "Transfusion strategies for acute upper gastrointestinal bleeding". NEJM. 2013. 368(1):11-21.
PubMed Full text PDF

Clinical Question

• Is a restrictive transfusion strategy superior to a liberal transfusion strategy in patients with upper GI bleeds?

Conclusion

• Compared to a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper GI bleeding.

Major Points

• The restrictive strategy required significantly less transfusions, had a higher probability of survival at 6 weeks, less further bleeding, less adverse effects, and lower mortality compared to the liberal strategy group.
• Restrictive strategy= transfusion threshold of hemoglobin 7g/deL if hemodynamically stable

Study Design

• Randomized prospective trial
• Patients admitted to Barcelona hospital between June 2003 and December 2009
• Patients randomized by computer, randomization stratified based on presence or absence of liver cirrhosis
  • In the restrictive group, Hb threshold for transfusion was 7 g/dL, with target range for post-transfusion of 7-9 g/dL
  • In the liberal-strategy group, Hb threshold for transfusion was 9 g/dL, with target range for post-transfusion of 9-11 g/dL
• In both groups, 1 unit of red cells was transfused initially and the hemoglobin level was assessed after transfusion
• Transfusion protocol applied until discharge or death
• Transfusion allowed any time symptoms or signs related to anemia developed, massive bleeding occurred during follow-up, or surgical intervention was required.
• Only pRBCs were used
• Hb measured after admission and again q8h during the first 2 days and every day thereafter
  • Hb levels assessed when further bleeding suspected
• All patients had emergency gastroscopy within the first 6 hours with appropriate techniques to mitigate bleeding.

Population

Inclusion Criteria

• Age >18
• Melena and/or hematemasis (or bloody nasogastric aspirate)
• Consent to blood transfusion

Exclusion Criteria

• Massive GI bleed
• Lower GI bleeding
• ACS
• Stroke/TIA
• Symptomatic PVD
• Transfusion in the previous 90 days
• Recent trauma or surgery
• Decision by attending physician that patient should not get a specific therapy
• Rockall score (assessment of future bleeding risk) of 0 with hemoglobin > 12

Interventions

• Transfusion threshold set at hgb 7 with target range 7-9 vs hgb 9 with target range 9-11
• Emergency gastroscopy within the first 6 hours to perform appropriate treatment
  • Injection of adrenaline and multipolar electrocoagulation or application of endoscopic clips for
    • Nonvariceal lesion with active arterial bleeding
    • Nonbleeding visible vessel
    • Adherent clot
  • Omeprazole bolus of 80mg followed by a continuous IV infusion of 80 mg per 10 hour period for next 72 hours
    • Peptic ulcer
  • Continuous intravenous infusion of somatostatin 250 micrograms per hour and prophylactic antibiotic therapy with norfloxacin or ceftriaxone were administered at the time of admission and continued for 5 days.
    • portal hypertension suspected
  • band ligation with sclerotherapy
    • bleeding esophageal varices
  • injection of cyanoacrylate
    • Bleeding gastric varices

Outcomes

• Lower mortality with restrictive transfusion strategy 5% vs 9% (p=0.02)

Primary Outcomes

• Death from any cause in the first 45 days
  • Lower with restrictive strategy

95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02)

Secondary Outcomes

• Rate of in hospital hematemasis or melena with hemodynamic instability (SBP<100 mmHg and/or HR>100)
• 2 point fall in hemoglobin in 6 hours
• Number of patients requiring transfusion in each group

Subgroup analysis

• Cirrhotic patients
  • Lower mortality with restrictive strategy in Child's class A and B
  • No difference in Child's class C
  • No significant difference when all cirrhotics taken as a group
• Peptic ulcer disease
  • No significant difference

Criticisms & Further Discussion

• 1 unit of pRBCs was transfused up front in both groups. Therefore, there was no true conservative transfusion group. The study suggests that a transfusion threshold of hgb 7 is superior, but cannot definitively answer the question as all patients in the study received a transfusion.
• All patients received an EGD within 6 hours. This may not be always be achievable. The study findings may not be generalizable.
• Massive GI bleeds, which were excluded from the trial, are not defined
• Low risk of rebleeding were not included
• Massive exsanguinating hemorrhage were also excluded
• Study was not blinded and could have introduced bias

Funding

• No external funding