• Ability to walk 10 feet across a room without human assistance [ Time Frame: Measured 60 days after study entry ] [ Designated as safety issue: No ]
  

• Myocardial infarction or death [ Time Frame: in-hospital ] [ Designated as safety issue: No ]
  
• Postoperative complications (e.g., pneumonia, thromboembolism, stroke) [ Time Frame: In hospital ] [ Designated as safety issue: No ]
  
• Survival [ Time Frame: 60 day and long term up to 5 years ] [ Designated as safety issue: No ]
  
• Nursing home placement [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  
• Function (e.g., activities of daily living, instrumental activities of daily living, fatigue) [ Time Frame: 30 and 60 days ] [ Designated as safety issue: No ]
  

BACKGROUND:

Red blood cell transfusions are an extremely common medical intervention in both the United States and worldwide; over 11 million units of blood are transfused in the United States. Between 60 and 70 percent of all blood is transfused in the surgical setting. Despite the common use of red blood cell transfusions, the threshold for transfusion has not been adequately evaluated and is very controversial. A decade ago, the standard of care was to administer a peri-operative transfusion whenever the hemoglobin (Hgb) level fell below 10 g/dl (the "10/30 rule"). Concerns about the safety of blood, especially with respect to HIV and hepatitis, and the absence of data to support a 10 g/dl threshold led to the current standard of care, which is to administer blood transfusions based on the presence of symptoms, and not a specific Hgb/hematocrit level. However, there have not been any randomized clinical trials done with surgical patients that have tested the efficacy and safety of withholding blood until the patient develops symptoms, or the "10/30" approach to transfusion. Patients with underlying cardiovascular disease are at greatest risk of adverse effects from reduced Hgb levels.

DESIGN NARRATIVE:

This is a multi-center randomized trial to test the effectiveness of a transfusion strategy that maintains postoperative Hgb levels above 10 g/dl in improving patient outcome. This will be compared to the symptomatic transfusion strategy, a more conservative strategy, in which blood transfusion is withheld until the patient develops symptoms of anemia. Participants will be randomly assigned to one of the two transfusion strategies. The 10 g/dl threshold strategy will use enough red blood cell units to maintain Hgb levels at or above 10 g/dl through hospital discharge. Symptomatic transfusion strategy patients will receive red blood cell transfusions for symptoms of anemia, although transfusion is also permitted, but not required, if the Hgb level falls below 8 g/dl. Outcomes will include functional recovery (primary outcome: ability to walk 10 feet across a room without human assistance 60 days post-randomization), long-term survival, nursing home placement, and postoperative complications (e.g., death in hospital or within 30 days, pneumonia, myocardial infarction, thromboembolism, stroke). An estimated 2,600 patients from 25 centers will be randomized over a 3.5-year period. This will allow detection of a 16% relative risk reduction in the loss of ability to walk independently with a power of approximately 0.90. A pilot study conducted with 84 participants demonstrated the feasibility of the study.

Ambulation at 60 days is known to be highly predictive of ultimate functional outcome as well as of mortality at one year. Because inability to walk again has such important implications for quality of life, and because it is a common problem, it far outweighs the small risk of viral infection or other complications from transfusion in elderly patients. Also, this study will measure the frequency and 95% confidence intervals of the medical errors that are important in this patient population and are poorly documented in the literature. The medical errors that will be measured are the following: transfusion errors (e.g., blood transfusion to the wrong patient, mislabeling of samples for type and cross match, use of whole blood instead of packed red cells), failure to use thromboembolism prophylaxis, incorrect antibiotic prophylaxis, wrong site surgery, and femoral shaft fracture.

The trial will also evaluate the effect of transfusion threshold on postoperative risk of acute cardiac ischemia. The strategy will be to enhance surveillance for ischemic events by increasing the number of EKG and serum troponin measurements beyond those already called for in the original FOCUS protocol.

There is an ancillary study to the trial (R01 HL085706) to examine delirium as an outcome in a subsample of 200 patients. We will assess short-term (in hospital) and longer-term (after 30 days) severity of delirium.