TRANSFUSION STRATEGIES FOR ACUTE UPPER GASTROINTESTINAL BLEEDING

JOURNAL CLUB REVIEW BY EVE PURDY

VILLANUEVA, C., COLOMO, A., BOSCH, A., CONCEPCIÓN, M., HERNANDEZ-GEA, V., ARACIL, C., ... & GUARNER, C. (2013). TRANSFUSION STRATEGIES FOR ACUTE UPPER GASTROINTESTINAL BLEEDING. N ENGL J MED , 368, 11-21.

BACKGROUND• Acute UGI is a common emergency condition with high

morbidity and mortality

• 10% from all causes of bleeding• >50% from bleeding varices (associated with cirrhosis)

• Transfusion helpful in exsanguination but effect less clear in less severe bleeds

• Restrictive vs Liberal

• Few studies in GI bleeding• Rebound hypertension specific factor in bleeding varices• Reduce use of blood products

PURPOSE

To determine whether a restrictive threshold for red-cell transfusion in patients with AGI bleeding more safe and more effective than a liberal transfusion strategy.

In patients > 18 with hematemesis or melena presenting to the ED does treatment according to guidelines with a transfusion threshold < 7g (target range 7-9g) or >9g (target 9-11g) reduce death within 45 days.

PICOT QUESTION

STUDY DESIGN

Inclusions: hematemesis, melena or both

Exclusions: massive bleeding, ACS, vasculopathy, stroke, TIA, transfusion within 90 days, trauma/surgery, lower GI bleeding, a previous decision on the part of the attending physician that the patient should avoid specific medical therapy, Rockall score of 0 and HgB > 12

THOUGHTS?

IMPROVEMENTS TO STUDY DESIGN?

DID INTERVENTION AND CONTROL START WITH THE SAME PROGNOSIS?

• Group allocation: computer generated random numbers with sealed, consecutively numbered, opaque envelopes

• Concealed and randomized• Stratified by presence or absence of cirrhosis (clinical,

biochemical and U/S findings)

PROGNOSTIC BALANCE MAINTAINED? • No blinding BUT:

• Transfusion guidelines applied throughout hospital stay• ALL patients underwent endoscopy in < 6hrs• Appropriate treatment (PUD vs variceal)• No differential cointerventions it would seem• Clinical ability to transfuse if clinical signs of anemia…

unclear

OUTCOMES• Primary: rate of death from any cause within the first 45 days

• Secondary:

• rate of further bleeding: hematemesis or fresh melena with hemodynamic instability or fall of HgB > 2g

• rate of in-hospital complications: untoward events that necessitated active therapy or prolonged hospitalization

THOUGHTS?

GROUPS BALANCED AT END OF STUDY? • 32 withdrew or were withdrawn by study investigators

(equal in both groups)

• Analyzed using intention-to-treat analysis for remaining

RESULTS-HEMOGLOBIN AND TRANSFUSION

Restrictive Liberal

Lower hemoglobin in the 1st 24 hours

Higher hemoglobin the first 24 hors

Lower hemoglobin at discharge

Higher hemoglobin at discharge

51% not transfused 14% not transfused

1.5 units/ transfusion 3.7 units / transfusion

9% protocol violation 3% protocol violation

Hemoglobin 11.6 at day 45 Hemoglobin 11.7 at day 45

RESULTS-FURTHER BLEEDING AND COMPLICATIONS

Restrictive Liberal

10% further bleeding 16% further bleeding

Shorter hospital stay (9.6) Longer hospital stay (11.5)

40% adverse events 48% adverse events

RESULTS- MORTALITYRestrictive Liberal

5% at 45 days 9% at 45 days

Virtually unchanged after adjustment for baseline risk factors (HR= 0.55 [0.33-0.92])

Significantly improves outcomes in patients with class A and B cirrhosis but unchanged in class C cirrhosis

HOW CAN I APPLY THE RESULTS?

BUT!

TAKE HOME MESSAGES• Well designed study with convincing results that restrictive

transfusion studies provide better outcomes then liberal transfusion studies in UGI bleeds

• Better control of further bleeding, rescue therapy and adverse events

• Plausible mechanisms in discussion: transfusion counteracts splanchnic vasoconstrictive response in hypovolemia and may impair clot formation

• Drawbacks

• Unblinded- but very objective outcomes• Physicians were able to override transfusion protocol (<10% in

each group)• Cannot be generalized to those with low risk of bleeding or those

with massive bleeding• More studies needed to see if >6hrs to endoscopy affects results

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