Tuesday, January 29, 2013

Special (Medical) Transfusion Situations

The Gist:  There are myths and uncertainty surrounding transfusion of packed red blood cells (PRBCs) in certain circumstances.  Lactated Ringer (LR) may not be a problem and old blood may not be as bad as we've thought (evidence is not impressive for either argument).  We've moved to restrictive transfusion strategies (hb <7.0) in many of the critically ill medical patients.  This philosophy is now creeping into other realms such as upper GI bleed and ACS, where dogma has traditionally demanded a higher trigger for transfusion. 

Lactated Ringer (LR) running during transfusion?  Probably fine.  On an exam, PRBCs shouldn't run with anything but normal saline and a few select medications.  Most hospitals and blood banks also state that LR and PRBCs are not compatibile.  Studies are popping up, however, that indicate that the idea of clot formation (from the amount of calcium in LR compared with the citrate in PRBCs) with this infusion may not be a major risk.  Check out this editorial that evaluates these recommendations.
  • Albert et al 
    • Simulation of intraoperative blood transfusion using units of PRBCs and either NS or R, as well as filters to analyze clots. RL did not lead to visible or molecular evidence of activation of the clotting cascade
  • Cull et al
    • PRBCs diluted with LR or normal saline (NS) in ratios between 5:1 to 1:20 (PRBC to crystalloid) and examined for clot formation at intervals up to two hours at body temperature. Although clotting occurred at dilutions of 1:1 (PRBC to LR) and greater, no clot formation occurred in the clinically relevant dilutions between 5:1 and 2:1
    • No difference in flow rates between PRBC diluted with LR or NS
  • Lorenzo et al Am J Surg
    • PRBC or whole blood (WB) (n=51) mixed with NS, lactate solution and LR solutions
    • No significant differences in infusion time or filter weight using WB or PRBC with NS or LR  
    • No significant difference in clot formation between NS and LR with WB or PRBC


Does transfusion improve tissue oxygenation?  
  • Rivers surviving sepsis study demonstrated benefit for PRBC transfusion (up to a HCT of 0.30) in an algorithm, which included a goal of achieving a ScVO2 of 70% in study subjects. Patients achieving this goal had better outcomes than did patients who did not reach the goal. The specific effect of transfusion was not evaluated in this study, since the study’s purpose was to evaluate the entire algorithm, and ScVO2 is not a patient-oriented outcome.
Is old blood bad blood?  It's probably not quite as good as fresh RBCs but this issue is complicated by:
  • A changing, unpredictable, and scarce supply of PRBCs 
  • Not knowing a precise, consistent point where benefit outweighs risk (for both the patient and the community served by the blood-bank) 
  • Patient factors. Lelubre et al did a review and basically couldn't find a solid difference between old blood and fresh blood.
Tintinalli says old blood is associated with poorer outcomes, using a study by Zallen et al (Ch 26). What is this based on?
  • Microcirculatory changes - laboratory studies have shown that older RBCs may be more fragile and less pliable, resulting in vasoocclusion (ref).
  • Fitzgerald et alDietrich et al, and Tsai et al proposed that RBCs a few weeks old may not have the same oxygen carrying capacity.
    • It's proposed that this is secondary to decreased 2,3 DPG. Remember that 2,3 DPG helps facilitate the unloading of O2 into tissues. 

http://upload.wikimedia.org/wikipedia/commons/8/8a/Oxyhaemoglobin_dissociation_curve.png 
(Wikimedia commons)
  • A study by Walsh et al demonstrated no difference in measurements of oxygen carrying capacity.
  • A blinded trial in septic patients by Lebiedz et al (2012) found that PRBCs >1 week old were associated with a poorer outcome. 
  • However, this data is sketchy. Check out Flegel 2012 for a counterpoint. RECESS, ABLE, and TRANSFUSE are 3 randomized trials currently underway (ref).
What about patients with an Upper GI Bleed? This has been all over the FOAM world since Villanueva et al was published in the NEJM in Jan 2013 demonstrating a mortality benefit in a restrictive transfusion strategy in UGIB (<7g/dL)

How About Cardiac Disease? Traditional teaching recommends a higher hemoglobin as a "transfusion trigger" than in other patient populations, which is plausible given ischemia and potential pump problems. Recently, some literature has come out that these patients probably don't need automatic transfusions with a hb of 9-10 g/dL, but there is insufficient data to recommend a good trigger point. Perhaps, however, less is more. This is a popular topic and more studies will be out soon!

Yang et al (2005)
  • n = 85,111 with NSTE ACS, observational study, mean transfusion nadir HCT 26%(8.6 g/dL).  
  • LOS- higher in transfused group 7 days (5.0-11.0) vs. 4 days (2.0-5.0). 
  • Absolute rate of death higher in transfused group (11.5% vs. 3.8%)
  • Death or MI combined higher in transfused group (13.4% vs. 5.8%)
  • Adjustment for patient and hospital characteristics - transfused patients remained 67% more likely to die and 44% more likely to experience either death or MI than those who did not undergo transfusion.
  • Limitations:  observational study, statistical adjustments, records review (data dredge).
Meta-analysis by Chatterjee et all (2012)
  • Included 10 studies, n=203,665
  • Mortality in transfused vs non-transfused 18.2% vs 10.2% (weighted absolute risk increase of 12% or a number needed to harm of 8)
    • No mortality difference in studies that included patients with STEMI (RR, 2.89; 95% CI, 0.54-15.58; P = .22) 
    • No mortality difference in patients with a baseline hematocrit of less than 30% (RR, 1.72; 95% CI, 0.39-7.63;P = .47). Note: few studies satisfied this.
  • Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (RR, 2.04; 95% CI, 1.06-3.93; P = .03
  • Limitations: almost all were observational studies, only 1 was an RCT. Few reported baseline hemoglobin levels and those that did varied widely (8-11 g/dL).

Sickle Cell? These patients live with low hb so a 7 g/dL transfusion trigger may not really apply to this population. Patients with sickle cell typically receive many transfusions throughout their life. This increases their risks of adverse effects from transfusions (and can make it more difficult to find usable blood).  These are the recommendations from the NIH and this literature review. There are controversial indications (complicated pregnancy, limb ulcers, refractory priapism), but these are generally outside the realm of EM.
Transfuse:
  • The bad stuff we see in the ED:
  • Before surgery requiring general anesthesia 
Don't need to transfuse: 
  • Clinically stable patients with high reticulocyte count 
  • Typical pain crises (there's some data, scant as it is, that transfusions could exacerbate a pain crisis)
Brain Injury  A recent review in Current Opinion in Critical Care  suggests that the restrictive transfusion strategy does not benefit patients with acute brain injury (perhaps may be harmful) but states that there is insufficient data to recommend a specific transfusion strategy in these situations.  LeRoux makes the following statements in the article
  • SAH - theoretical benefit and a study shows improved oxygenation but some studies show increased vasospasm.
  • TBI - Limited data suggest transfusion only with symptomatic anemia.
  • Acute ischemic stroke - no sign that  PRBCs help
Updated 2/12/13

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