Transfusion in Critical Illness

Thanks to Dave and Heather Collins for a highly entertaining evening, and to J Beckemeyer, Catherine, Elise, Erin, J Remke and Dr. Febbo for their erudite presentations.

Increasingly, data support a more restrictive approach to blood transfusion.  Think of a blood transfusion as a liquid organ transplant, with added risks of TACO, TRALI and other transfusion related immunomodulation. 

BOTTOM LINE FOR JOURNAL CLUB:  7 is the new 10, and 1 is the new 2.  Transfuse at a hemoglobin of 7 g/dl unless unstable/actively hemorrhaging or having ACS, and give 1 unit of pRBCs at a time.  For ACS, current literature is inconsistent but reviewed article favored the more traditional approach of transfusing to 10 g/dl. 

1.     Villanueva C, et al. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013; 368:11-21.

In this single center RCT of 921 patients with acute upper GI bleeding, half were randomized to a restrictive strategy (transfuse when hemoblobin < 7 g/dl) and half to a liberal strategy (transfuse when hemoglobin < 9 g/dl).  Patients were included if >18 yo and evidence of acute upper GIB by hematemesis, melena, or both.   Patients with massive exsanguinating bleeding, ACS, symptomatic PVD, and TIA/CVA were excluded.  They also excluded patients with Rockall scores of zero and hemoglobin >12 (wimpy bleeds).  Randomization was stratified according to presence/absence of cirrhosis.  Transfusions were given 1 unit at a time, with reassessment.  Transfusion could also be given for symptomatic anemia, massive bleeding, or need for surgical intervention.  All patients underwent endoscopy within 6 hours.

Primary outcome of survival at 6 weeks was significantly higher in the restrictive (95%) versus liberal (91%) group.  Risk of further bleeding, adverse events, and rescue therapies were significantly lower in the restrictive group. Patients in the liberal group also had significant early rises in portal-pressure gradient (increases risk of rebleeding).  The only subgroup without a significant mortality difference were patients with advanced cirrhosis.

Why does restrictive strategy work in GI bleed?  Authors posit that transfusion may counteract protective splanchnic vasoconstrictive response caused by hypovolemia.  This increased pressure may impair clot formation.  Transfusion may also induce coagulation abnormalities, and for patients with cirrhosis, increased blood volume can increase portal pressure leading to rebleeding.

BOTTOM LINE:  great study looking at a population that makes us nervous, supporting a restrictive transfusion strategy to improve mortality, decrease rebleeding/adverse events, and conserve resources.  It’s a win/win, but remember that they excluded patients with exsanguinating bleeding as well as those with ACS.  Also, transfusion could be given for symptomatic anemia, massive bleeding, or if need for surgery-important caveats.  Finally, these patients all underwent early endoscopy, facilitating early intervention for ulcer, varices, etc.


2.     Holst LB, et al:  Lower versus higher hemoglobin threshold for transfusion in septic shock.  N Engl J Med  2014 9;371(15):1381-91. 

In this multicenter, randomized trial, 998 ICU patients with septic shock were randomized to a lower threshold group (transfuse 1 unit pRBCs for hemoglobin < 7 g/dl) or higher threshold group (transfuse 1 unit pRBCs for hemoglobin < 9 g/dl). 

Patients with stable cardiovascular disease were included, but patients with life threatening bleeding or ACS were excluded.  Patients developing life threatening bleeding, ischemia, or need for ECMO or surgery after enrollment could receive transfusion at discretion of treating physician.  Leukoreduced blood was used in an attempt to mitigate immunomodulatory effects of transfusion.

Primary outcome of death by 90 days occurred in 43% of lower threshold group compared with 45% of higher threshold group (RR 0.94; 95% CI 0.78-1.09).  Rates of ischemic events, severe adverse reactions, and life support requirements were also similar in the two groups.  The lower threshold group received half the total number of transfusions as the higher threshold group.  It’s an ICU, not an ED study, but given our boarding, probably still pretty useful information.

BOTTOM LINE: in ICU patients with septic shock, similar mortality and adverse event rates were observed with a lower transfusion threshold (transfuse for hemoglobin < 7 g/dl), with significant savings in the number of units of blood transfused.


3.     Carson JL, et al: Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J  2013;165(6):964.

Ok, so clear that in GI bleed and sepsis (and from the unfortunately named TRICC trial, for critically ill patients in general) a more restrictive blood transfusion strategy is safe and effective.  The holy grail remains...what about patients with ACS??

In this “pilot trial” of 110 patients with ACS or stable angina undergoing cardiac cath, patients were randomized to receive transfusion for hemoglobin < 10 g/dl (liberal strategy), or to transfusion for symptomatic anemia as well as permitted/not required to receive transfusion for hemoglobin < 8 (restrictive strategy).

Patients with active bleeding, hemodynamic instability, symptomatic anemia at time of randomization, or needing surgery were excluded.

Primary outcome was the composite of death, MI, or unscheduled revascularization 30 days after randomization, and occurred in 11% of liberal group and 25.5% of restrictive group (95% CI 0.7% – 29%).  Death at 30 days was 2% in liberal group vs. 13% in restrictive group (95% CI 1.5% – 21%).  These were not significant differences due to small group sizes/large CI, but trends favored liberal transfusion strategy.  All deaths were classified as cardiac.  Most other adverse cardiac outcomes were more frequent in restrictive group.

This study had problems.  First, it’s a small study, so can’t draw practice-changing conclusions.  Also, the restrictive group was on average 7 years older than the liberal group.  Patients with ACS are different from those with stable disease undergoing cath-really these are 2 separate populations.  The study was terminated prior to completing their planned enrollment of 200 patients...not clear why...they do some hand waving about having enough information to plan a larger trial.  Interestingly, the most frequent reason for protocol violation was insufficient time to administer transfusion prior to discharge in the liberal group (wait Mr. Smith...don’t call a taxi yet, let’s give you an [unnecessary?] transfusion).

BOTTOM LINE:  Not a great study, but trends support a more liberal strategy (transfuse for hemoglobin < 10) in patients with ACS. Existing literature for this population is inconsistent, equipoise exists, and a large, well done study still needs to be performed.