Villanueva C, Colomo A, Bosch A Iet al.
Aim of Study
Stated hypothesis: A restrictive threshold for red-cell transfusion in patients with acute GI bleed is safer and more effective than a liberal transfusion strategy.
Design and Location
Randomised control trial in Barcelona, Spain.
Random assignment on admission to hospital to restrictive (transfusion threshold 7g/dl) or liberal (transfusion threshold 9g/dl) blood transfusion strategy with stratification for presence or absence of cirrhosis.
Rate of death from all cause within first 45 days.
Rate of further bleeding and rate of in hospital complications.
Power calculation based on a two-tailed test with alpha and beta values of 0.05 and 0.2 respectively. Intention-to-treat. Kaplan-Meier method and log-rank test. Cox proportional-hazards regression model.
- Mortality at 45 days was significantly lower in the restrictive-strategy group than in the liberal-strategy group: 5% (23 patients) as compared with 9% (41 patients) (P=0.02).
- Rate of further bleeding was significantly lower in the restrictive-strategy group than in the liberal-strategy group: 10% (45 patients), as compared with 16% (71 patients) (P=0.01).
- Patients with cirrhosis risk of further bleeding was lower with the restrictive transfusion strategy than with the liberal transfusion strategy among patients with Child–Pugh class A or B disease and was similar in the two groups among patients with Child–Pugh class C disease.
- Patients in the liberal-strategy group had a significant increase in the mean hepatic venous pressure gradient between the first hemodynamic study and the second (from 20.5±3.1 mm Hg to 21.4±4.3 mm Hg, P=0.03).
- There was no significant change in mean hepatic venous pressure gradient in the restrictive-strategy group during that interval.
- The overall rate of complications was significantly lower in the restrictive-strategy group than in the liberal-strategy group (40% [179 patients] vs. 48% [214 patients], P=0.02), as was the rate of serious adverse events
Outcomes in patients with severe acute upper gastrointestinal bleeding were significantly improved with a restrictive transfusion strategy.
The harmful effects of transfusion may be related to the counteraction of splanchnic vasoconstrictive response caused by hypovolemia, inducing an increase in splanchnic blood flow and impairment in clots formation. Transfusion may also induce coagulation abnormalities. Beneficial effect of a restrictive transfusion strategy with respect to further bleeding was observed mainly in patients with portal hypertension. Liberal-strategy group had a significant increase in portal pressure during acute variceal bleeding that was not observed in patients in the restrictive-strategy group possibly accounting for the higher rate of further bleeding with the liberal strategy.
Stated Limitations from the Study
Main limitation was that all patients in the study had an OGD within 6 hours of admission.
In addition to this:
- Power calculation assumed mortality of 10%, actual mortality less than 10%,
- Co-existing conditions were not included in analysis or randomisation so the presence of these conditions may account for discrepancies in complication rate,
- Mean blood storage time for blood was 15 days, with storage lesions possible from 14 days so higher transfusion amount will expose patients to more storage lesions,
- Violation of protocol higher in restrictive group suggesting greater rates of symptoms related to anaemia.
Discussion from Journal Club Meeting (?Change of Practice)
Discussed higher rates of protocol violation in the restrictive group, lack of data in study on other fluid administration, routine practice at Kingston and considering “therapeutic illusion” when considering treatment. Paper adds to the ICU and Trauma evidence that restrictive transfusion strategies are at least as safe if not more effective than liberal transfusion strategies in acute blood loss and is worth considering when managing acute blood loss.
Summary by Dr J Lambert. Journal Club Meeting 04 July 2019.