Transfusions in Acute Care Too Little?

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Transfusions in Acute Care Too Little? Keyvan Karkouti MD FRCPC MSc Associate Professor Department of Anesthesia; Department of Health Policy, Management, and Evaluation; University of Toronto Scientist Toronto General Research Institute

Galileo Galilei

Low Transfusion Triggers Based primarily on the landmark TRICC study

TRICC Trial Design Euvolemic, non-bleeding patients with Hb 9.0 g/dl within 72 hours of admission to ICU Randomized to Restrictive strategy: RBC if Hb < 7.0 g/dl, to maintain at 7.0-9.0 g/dl Liberal strategy: RBC if Hb <10.0 g/dl, to maintain at 10.0-12.0 g/dl

TRICC Trial Result

TRICC Trial Conclusion In most critically ill patients, the red-cell transfusion trigger should be 70 g/l With the possible exception of patients with active coronary ischemic syndromes

Assume That TRICC Findings are Fully Valid Ignore potentially important design limitations Unblinded Allowed for multiple transfusions in euvolemic patients Used fixed transfusion triggers Practice misalignment among: 1 Patients with mild disease randomized to liberal arm (unnecessarily exposed to risks of treatment) Patients with severe disease randomized to restrictive arm (unnecessarily exposed to risks of anemia) 1. Deans et al. Crit Care Med 2007;35:109-1516

To Whom Do the Results Apply?

To Whom Do the Results Apply?

Who are The Other 90%? Not euvolemic Actively bleeding Chronic anemia Cardiac surgery Physician refusal Those in whom Hb 70 g/l deemed unsafe? Other reasons

What about The Other 90%?

What about The Other 90%?

What about The Other 90%? Does the one-size-fits-all approach to anemia make sense? Can they all tolerate a Hb of 70 g/l?

Anemia Tolerance: One Size Does Not Fit All Normal Hb varies by gender, race, etc. Women Men Patel et al. Blood 2007; 109:4663-4670

Anemia Tolerance: One Size Does Not Fit All Anemia s prognostic value also varies by gender, race, etc. Patel et al. Blood 2007; 109:4663-4670

Anemia Tolerance in CVS Adjusted OR = 1.1 (0.8 1.6) P = 0.4 Karkouti et al. Transfusion 2008;48:666-672

Anemia Tolerance in CVS Adjusted OR = 1.5 (1.1 2.1) P = 0.007 Karkouti et al. Transfusion 2008;48:666-672

ACS Anemia and Mortality in STEMI Sabatine et al. Circulation 2005; 111:2042

ACS Anemia and Mortality in STEMI RBC α Death if Hb < 12 OR 0.42 (0.20 0.89) Sabatine et al. Circulation 2005; 111:2042

ACS Anemia and Mortality in NSTEMI Sabatine et al. Circulation 2005; 111:2042

ACS Anemia and Mortality in NSTEMI RBC α Death OR 1.5 (1.1 2.1) Sabatine et al. Circulation 2005; 111:2042

CVS Intraoperative Anemia and AKI Acute Renal Failure (%) < 21% 21-25% > 25% Nadir Hct Karkouti et al. J Thorac Cardiovasc Surg 2005;129:391

Anemia and Coagulopathy Valeri et al. Transfusion 2001;41:977-83

Anemia and Coagulopathy Valeri et al. Transfusion 2001;41:977-83

What about The Other 90%? Does the one-size-fits-all approach to anemia make sense? Can they all tolerate a Hb of 70 g/l?

What about The Other 90%? Does the one-size-fits-all approach to anemia make sense? Can they all tolerate a Hb of 70 g/l? No

What about The Other 90%? Does the one-size-fits-all approach to anemia make sense? Can they all tolerate a Hb of 70 g/l? No When is 70 not 70?

When is 70 not 70? 1 hour PT 24 hours PT 0 to 10 day old blood 25 to 35 day old blood Luten et al. Transfusion 2008;48:1478-1485

What then, should the transfusion trigger be?

What then, should the transfusion trigger be? Non-bleeding, euvolemic patient The only indication for RBC transfusion is to increase oxygen delivery to tissues in the setting of tissue hypoxemia* Varies from patient to patient Varies from organ to organ Varies from setting to setting Difficult to recognize May occur at Hb > 70 g/l *Consensus Conference. Perioperative red blood cell transfusion. JAMA 1988;260:2700

What then, should the transfusion trigger be? Bleeding patient More complex? Volume status: fluctuating and rarely euvolemic Amount of blood lost Expectations for ongoing blood loss Number of red-cells transfused Or is it all very simple? Trigger Hb 100 g/l as part of goal-directed therapy E.g., Rivers et al. NEJM 2001; 345:1368-77

Transfusion Triggers: Current Algorithms ASA Algorithm for RBC Transfusion Monitor for blood loss Monitor for inadequate perfusion and oxygenation of vital organs Monitor hemoglobin Hb > 100 g/l transfusion is usually unnecessary Hb < 60 g/l transfusion is usually necessary Hb 60 100 g/l transfusion depends on 1 and 2

What about other blood products? ASA Algorithm for Cryoprecipitate Fibrinogen > 150 mg/dl transfusion rarely indicated Fibrinogen < 80-100 mg/dl transfusion usually indicated

Conclusions Don t consider established transfusion practice or guidelines as established Likely based on limited, faulty, or inapplicable data The transfusion decision is, by necessity, complex Cannot be based on simplistic triggers

Thank You