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Transfusion of Blood Products for Sepsis and Septic Shock
*PulmCCM is not affiliated with the Surviving Sepsis Campaign.
People with severe sepsis and septic shock frequently experience what could be termed "hematologic failure" -- abnormalities of blood cell lines and clotting / antithrombotic proteins that can occur in complex, protean patterns. Anemia, thrombocytopenia, leukopenia, disseminated intravascular coagulation, and functional deficiencies of coagulation factors are all common in people with severe sepsis or septic shock. Clinically evident bleeding or thrombosis caused by these derangements is unusual, and supportive care has been advised for most critically ill patients with hematologic abnormalities, with transfusion in selected severe cases.
Red Blood Cell Transfusions in Sepsis and Septic Shock
Anemia is common in medical patients and nearly universal in patients with critical illness lasting more than a day or 2. Although many hospitals' sepsis protocols include transfusion of packed red blood cells to a hematocrit of 30% for patients with central venous oxygen saturation < 70% (mixed venous < 65%) after establishment of a mean arterial pressure of 65 mm Hg (based on the original Rivers study), this intervention has been challenged in light of evidence that red blood cell transfusion can be harmful to critically ill patients.
Packed red blood cell transfusion in early goal directed therapy for severe sepsis and septic shock did not make it into the latest Surviving Sepsis Guidelines as a graded recommendation. Rather, blood transfusion as part of EGDT for severe sepsis / septic shock is considered an "option" co-equal with dobutamine infusion to improve perfusion:
During the first 6 hrs of resuscitation, if ScvO2 less than 70% or SvO2 equivalent of less than 65% persists with what is judged to be adequate intravascular volume repletion in the presence of persisting tissue hypoperfusion, then dobutamine infusion (to a maximum of 20 μg/kg/min) or transfusion of packed red blood cells to achieve a hematocrit of greater than or equal to 30% in attempts to achieve the ScvO2 or SvO2 goal are options.
After adequate tissue perfusion has been restored with resuscitation fluids and vasopressors (ideally within the first 6 hours of recognition of severe sepsis, for most patients), a restrictive approach to red blood cell transfusion is recommended, as with almost all critically ill patients.
The Surviving Sepsis Guidelines advocate restricting red blood cell transfusion in adults with severe sepsis/septic shock until hemoglobin falls below 7.0 g/dL, and not transfusing above 9.0 g/dL, if ischemic heart disease, severe hypoxemia, or active bleeding are not present. (Grade 1B)
Erythropoietin Not Advised as Treatment for Anemia from Sepsis/Septic Shock
Erythropoietin hasn't been studied in septic patients, but it has in critically ill patients in general, in whom anemia is nearly universal after a few days in the ICU. Erythropoietin or EPO tends to reduce the need for red blood cell transfusion during critical illness, but has had no demonstrated effect on clinical outcomes. Although certain patients with severe sepsis and septic shock may have other reasons to receive erythropoietin, the Surviving Sepsis Guidelines advise against giving erythropoietin as treatment for anemia associated with severe sepsis / septic shock. (Grade 1B).
Don't Transfuse Fresh Frozen Plasma Prophylactically in Sepsis/Septic Shock
No clinical studies have been done to determine whether correcting coagulation abnormalities (elevated prothrombin time / INR) with transfusion of fresh frozen plasma (FFP) affects outcomes in severe sepsis and septic shock. However, neither are there any studies that show that correction of coagulation abnormalities helps any patients who are not bleeding, even if their INR is severely elevated.
Given this absence of any demonstrated benefit, the Surviving Sepsis Guidelines suggest reserving transfusion of fresh frozen plasma (FFP) for those patients with severe sepsis/septic shock who have increased PT, PTT, and/or INR, and who either have active bleeding, or are planned to undergo surgery or invasive procedures. (Grade 2D).
When to Transfuse Platelets in Severe Sepsis/Septic Shock
Platelet transfusion guidelines in severe sepsis and septic shock are based on consensus opinion, largely deriving from oncologists' experience managing non-septic patients' chemotherapy-induced thrombocytopenia, largely due to suppressed platelet production. Thrombocytopenia in sepsis is due both to impaired platelet production and also increased platelet destruction. There is no solid evidence to guide platelet transfusion in severe sepsis and septic shock, but a restrictive approach is suggested, unless bleeding or the risk thereof is present.
For patients with severe sepsis and septic shock, the Surviving Sepsis Guidelines suggest transfusing platelets prophylactically only when platelets fall to 10,000 / mm3, assuming no bleeding is present. In patients considered at significant risk for bleeding, a threshold of 20,000 / mm3 is suggested, and for those with active bleeding or who are undergoing surgery or invasive procedures, transfusing platelets to 50,000 mm3 is suggested. (Grade 2D).
Which patients with severe sepsis and septic shock are at "significant" elevated risk of bleeding? The authors of the Surviving Sepsis Guidelines suggest that many are, including those with fevers, other coagulation abnormalities, recent bleeding (even if minor), rapid fall in platelet concentration, and who have had recent chemotherapy. They imply that if severe thrombocytopenia is present, these patients should be considered for prophylactic platelet transfusion to thresholds above 20,000 / mm3 .
No Antithrombin III for Severe Sepsis / Septic Shock
A large Phase 3 randomized trial (n=2,314) showed high-dose antithrombin III had no effect on 28-day mortality in people with severe sepsis or septic shock. Subgroup analyses suggested potential benefit among the sickest patients and those not also receiving heparin. However, the disappointing negative trial led Aventis Behring to shelve antithrombin III as an investigational treatment for septic shock, perhaps permanently. The Surviving Sepsis Guidelines advise against the use of antithrombin III for severe sepsis or septic shock. (Grade 1B).
Guide to Recommendations’ Strengths and Supporting Evidence in the Surviving Sepsis Guidelines:
- 1 = strong recommendation;
- 2 = weak recommendation or suggestion;
- A = good evidence from randomized trials;
- B = moderate strength evidence from small randomized trial(s) or upgraded observational trials;
- C = low strength evidence, well-done observational trials with control randomized controlled trials
- D = very low strength evidence, downgraded controlled studies or expert opinion.