Page 1236 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 89: Anemia and Red Blood Cell Transfusion in Critically Ill Patients 843

RED BLOOD CELL TRANSFUSION IN CRITICAL ILLNESS goal-directed therapy in patients presenting with septic shock. 12,21 The
protocol included recommendations for RBC transfusions for Hb less
It seems clear that hemoglobin levels falling significantly below the than 10 g/dL if central venous oxygen saturation was below 70% after
“10/30” threshold can be tolerated by individuals who are not critically establishing hemodynamic stability and euvolemia. Although there was
ill. However, whether this is applicable to all critically ill patients has been a significant reduction in mortality in the patients who received the
questioned. The best evidence available regarding the efficacy of RBC goal-directed therapy (including more RBC transfusions), the contribu-
transfusion in critically ill patients is the randomized controlled trial tion of RBC transfusion, if any, is difficult to evaluate as there were mul-
12
(TRICC trial) by Hebert et al. The TRICC trial enrolled 838 critically tiple interventions being studied simultaneously. In fact, a more recent
ill euvolemic patients with Hb less than 9 g/dL and compared a liberal rial studying the effect of transfusion alone did not detect a benefit for
transfusion strategy (Hb 10-12 g/dL) to a restrictive transfusion strat- liberal transfusion in patients with severe sepsis.
egy (Hb 7.0-9.0 g/dL). Patients in the liberal transfusion arm received
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significantly more RBC transfusions. Overall in-hospital mortality was
significantly lower in the restrictive strategy group, although the 30-day TRANSFUSION-RELATED IMMUNOMODULATION
mortality rate was not significantly different. However, in those patients AND AGE OF TRANSFUSED RBCs
who were less ill (APACHE <20) or younger (<55 years of age), the
30-day mortality rates were significantly lower for the patients in the As noted above, anemia is very common in the critically ill with almost
restrictive transfusion group. Further subgroup analysis demonstrated 95% of patients admitted to the ICU having an Hb below normal by ICU
no mortality difference between a liberal and restrictive strategy in day 3. As a consequence of this anemia, critically ill patients receive a
patients with septic shock, trauma, or primary or secondary cardiac large number of RBC transfusions. This has been well documented in two
disease. Therefore, a restrictive strategy is at least equivalent and possi- cross-sectional studies of RBC transfusion practice, one conducted in
12
bly superior, in some patients, to a more liberal transfusion strategy. This Europe and the other in the United States. 22,23 These studies demonstrated
concept was recently reviewed by the Cochrane Collaboration in 2010. almost identical results, with approximately 40% of ICU patients trans-
13
This review of 19 trials involving 6264 patients confirmed a reduction fused on average almost 5 units of RBCs while in the ICU. Both studies
in hospital mortality (although not 30-day mortality) with a restrictive also noted an increase in mortality associated with RBC transfusion.
strategy. There was no difference in adverse events observed. Although A recent systemic review of the literature on RBC efficacy (45 studies
the benefit of a restrictive strategy was supported in patients with pre- including 272,596 patients) demonstrated that RBC transfusion
existing cardiovascular disease, the available trials were not sufficient was associated with increased mortality and morbidity, including infec-
to draw conclusions on patients with acute coronary syndromes (ACS). tious and respiratory complications. 24
Acute coronary syndromes are constellation of diseases defined as non- Two explanations have been suggested to explain the apparent lack of
ST elevation myocardial infarction (NSTEMI), ST elevation myocardial benefit from RBC transfusions. The first explanation is that the adverse
infarction (STEMI), and unstable angina. Recommendations for this group clinical consequences of RBC transfusion result from the effects of leu-
have been unclear because of conflicting data and the absence of a defini- kocytes contained in the transfused blood. The second explanation is
tive clinical trial. 14-19 Taken together the studies suggest that there is an Hb that the adverse clinical consequences of RBC transfusion result from
below which RBC transfusion improves outcome; on the other hand, there prolonged red cell storage, i.e., transfusion of “old” RBCs.
is an Hb level above which RBC transfusion worsens outcome. What those Several studies have suggested that blood transfusions depress
Hb levels are, is not clear. Wu et al retrospectively studied Medicare records immune function in a recipient. Recent meta-analyses and reviews of
25
of 78,974 patients older than age 65 who were hospitalized with a primary the randomized trials do not provide convincing evidence for or against
15
diagnosis of acute myocardial infarction. Lower admission HCT were the potential role of leukoreduction in decreasing mortality or post-
associated with increased 30-day mortality with a mortality rate approach- operative infections. At this juncture, evidence would suggest that, at
26
ing 50% among patients with an HCT of 27% or lower who did not receive most, removal of leukocytes from RBC transfusions may have a small
an RBC transfusion. RBC transfusion was associated with a reduction in but potentially important effect on clinical outcomes following critical
30-day mortality for patients who received at least one RBC transfusion illness. While there is certainly no negative impact from leukoreduc-
27
if their admitting HCT was less than 33% while RBC transfusion was tion, the overall cost-effectiveness of universal leukoreduction has yet to
associated with increased 30-day mortality for patients whose admitting be proven, especially in lower risk populations. In addition, the recent
HCT values were 36.1% or higher. Finally, Rao et al analyzed the effect of studies suggest that the incremental benefits provided by leukoreduction
RBC transfusion on outcome in over 24,000 patients with ACS that had may not be mediated through immunomodulation but rather through
been enrolled in three clinical trials. This post hoc analysis found that decreased stimulation of the inflammatory cascade. 28
18
RBC transfusion in patients with ACS and a nadir HCT greater than 25 In 1992, Marik and Sibbald first demonstrated the potential harm
was associated with an increase in 30-day mortality, which persisted after from prolonged red cell storage by detecting an association between
adjusting for comorbidities. In contrast, Hebert et al reported results from a fall in gastric pHi, an indicator of poor flow and oxygenation of the
the subgroup of critically ill patients who had cardiovascular disease from bowel, and transfusion of RBCs stored for greater than 15 days. This
29
the TRICC trial finding no significant difference in mortality between study has stimulated a number of investigators to question whether old
the two transfusion strategies in patients with cardiovascular disease in RBCs are effective oxygen carriers. The determination of shelf life for
general. However, in the patients with severe ischemic heart disease, a red cells has been based upon the maintenance corpuscular integrity
20
trend toward decreased survival was observed in the group managed with and posttransfusion 24-hour survival rather than functional assays.
30
the restrictive strategy. This was the only subgroup in the study that favored A number of changes to the corpuscle and cytosol occur over time in
the liberal transfusion strategy. In summary, data currently available do not storage. During storage, RBCs undergo a predictable change in mor-
allow firm conclusions regarding RBC transfusion in the patient with ACS. phology, evolving from biconcave discs to deformed spheroechinocytes.
Further studies are required before definitive recommendation regard- These corpuscular changes are associated with a number of biochemical
ing anemia and transfusion practice in patients with ACS can be made. and biomechanical changes including a depletion of adenosine triphos-
However, patients with cardiovascular disease, but not ACS, are similar to phate (ATP) and 2,3-DPG, and loss of deformability. These corpuscular
other critically ill patients with regard to RBC transfusion. changes may contribute to adverse clinical consequences as a result of
Subgroup analysis of the TRICC trial, as well as other trials of RBC altered or diminished oxygen transport. Based on these observations, it
transfusion in established sepsis, demonstrated no difference in mortal- has been speculated that transfusion of large amounts of stored RBCs
ity between the restrictive and liberal transfusion groups for patients may have an adverse clinical consequence on O delivery in patients
2
with sepsis or severe sepsis. However, a possible role for RBC transfu- whose balance is compromised. However, this hypothesis has not
sion was raised in a subsequent trial by Rivers et al, examining early been tested in controlled clinical trials. Retrospective clinical studies

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