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Transfusion in SepsisTransfusion in Sepsis – The Controversy Continues

Red blood cell (RBC) transfusion in septic patients remains a controversial topic. The well-known and often quoted article by Rivers et al. in New England Journal of Medicine, 2001, was one of the first to attempt to define a protocol for transfusion along with primary use of fluid resuscitation, vasopressors and inotropic agents.¹

The assumption and hope of incorporating RBC transfusion into what was deemed “Early Goal-Directed Therapy” (EGDT) was that anemic septic patients would acquire an increased O₂ delivery during this critical timeframe.

Since publication of this single-center study, most intensivists have incorporated the protocol and this included RBC transfusion for Hct < 30%, particularly within the first 6 hours of sepsis onset. Unfortunately, it is difficult to truly identify which part of the EGDT had the most impact on outcome, morbidity and mortality.

The subsequent Surviving Sepsis Guidelines, published in 2008, made a dramatic impact with specific definitions of sepsis, including the definition of severe sepsis, and utilization of the GRADE method of evaluation for evidence for multiple interventions and clinical or laboratory targets.² This group commented on the controversy surrounding the actual ability of packed RBCs to increase O₂ and tissue perfusion. The article by Napolitano et al in Critical Care Medicine, in 2009, provided only Level 2 evidence supporting transfusion of RBCs in the septic patient and called for individual assessment prior to transfusion.³ In fact, this article’s review of several studies that measured the potential to increase DO₂ and/or VO₂ with transfusion of RBCs provides conflicting results.

Disparate results from other studies as to the positive or negative impact of transfusion in sepsis outcomes suffer from varied study designs, patient comorbidities, inclusion of only severely septic patients (by definition), age of RBCs transfused and the use of leuko-reduced products.⁴’⁵’⁶ In fact, there has been no clear consensus on how, or even if, the age of blood (or “storage lesion”) contributes to negative patient outcomes. Leuko-reduction could theoretically decrease the ability of the blood product to produce immunomodulatory effects, but much study is needed in this area as well.

The Surviving Sepsis Guideline was revised and re-published in 2013.⁷ This guideline states: “The transfusion threshold of 7 g/dL contrasts with early goal-directed resuscitation protocols that use a target hematocrit of 30% in patients with low Scvo2 during the first 6 hrs of resuscitation of septic shock.” The following list includes these most recently published recommendations for transfusion of blood components in septic patients. This list includes not only RBCs, but plasma and platelet transfusion criteria.

  1. Recommendation #1: Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, …recommend that red blood cell transfusion occur only when hemoglobin decreases to ≤ 7.0 g/dL to target a hemoglobin concentration of 7.0-9.0 g/dL in adults (grade 1B).
  2. Recommendation #2: Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).
  3. Recommendation #3: Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned procedure (grade 2D).
  4. Recommendation #4: Not using antithrombin for the treatment of severe sepsis and septic shock (grade 1B).
  5. Recommendation #5: In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/µL…in the absence of apparent bleeding. …suggest prophylactic platelet transfusion when counts are <20,000/µL…if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/µL)…are advised for active bleeding, surgery, or invasive procedures (grade 2D).

Therefore, in summary, patients with sepsis and frank septic shock are frequently transfused in our critical care units. The most recent recommendations are to individualize the approach to the treatment of these patients, supporting careful consideration of limited transfusion to transfusion at threshold of < 7.0 g/dL and target Hgb levels of 7-9 mg/dL. The authors acknowledge “(the) transfusion threshold of 7 g/dL contrasts with early goal-directed resuscitation protocols that use a target hematocrit of 30% in patients with low Scvo2 during the first 6 hrs of resuscitation of septic shock,” and support higher thresholds only when other measures to improve tissue oxygenation are unsuccessful. No doubt, the controversy continues and additional research is needed in this area of critical care.


  1. Rivers E et al. N Engl J Med, 2008; 345: 1368
  2. Dellinger R et al. Crit Care Med, 2008; 36: 296
  3. Napolitano L et al. Crit Care Med, 2009; 37: 3124
  4. Vincent J et al. Anesth, 2008; 108; 31
  5. Sakr Y et al. Crit Care, 2010; 14; R92
  6. Park D et al. Crit Care Med, 2012; 40: 1
  7. Dellinger R et al. Crit Care Med, 2013; 41:580
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