2015 Jan 14:1-10. [Epub ahead of print]
Background and purpose – Hip fracture (HF) in frail elderly patients is associated with poor physical recovery and death. There is often postoperative blood loss and the hemoglobin (Hb) threshold for red blood cell (RBC) transfusions in these patients is unknown. We investigated whether RBC transfusion strategies were associated with the degree of physical recovery or with reduced mortality after HF surgery. Patients and methods – We enrolled 284 consecutive post-surgical HF patients (aged ≥ 65 years) with Hb levels < 11.3 g/dL (7 mmol/L) who had been admitted from nursing homes or sheltered housing. Allocation was stratified by residence. The patients were randomly assigned to either restrictive (Hb < 9.7 g/dL; < 6 mmol/L) or liberal (Hb < 11.3 g/dL; < 7 mmol/L) RBC transfusions given within the first 30 days postoperatively. Follow-up was at 90 days. Results – No statistically significant differences were found in repeated measures of daily living activities or in 90-day mortality rate between the restrictive group (where 27% died) and the liberal group (where 21% died). Per-protocol 30-day mortality was higher with the restrictive strategy (hazard ratio (HR) = 2.4, 95% CI: 1.1-5.2; p = 0.03). The 90-day mortality rate was higher for nursing home residents in the restrictive transfusion group (36%) than for those in the liberal group (20%) (HR = 2.0, 95% CI: 1.1-3.6; p = 0.01). Interpretation – According to our Hb thresholds, recovery from physical disabilities in frail elderly hip fracture patients was similar after a restrictive RBC transfusion strategy and after a liberal strategy. Implementation of a liberal RBC transfusion strategy in nursing home residents has the potential to increase survival.
This randomized trial found, in contrast to almost all trials of restrictive transfusion triggers, that in a subset analysis of nursing home residents with hip fracture, the liberal transfusion strategy yielded much lower mortality than the restrictive trigger. The restrictive trigger, (9.7 g/dl) would be considered liberal in most studies, which is one problem. That transfusing patients with a liberal trigger of 11.3 g/dl threshold would actually reduce mortality in patients conflicts with virtually everything we have learned about transfusion therapy over the last 10-15 years. There is no evidence in any patient population that maintaining a hemoglobin above 10 g/dl would actually improve clinical outcomes, so that is one reason for being cautious about these results. Indeed, almost every study done to date with a trigger that high has had inferior clinical outcomes to the restrictive group with triggers in the 7-8 g/dl range. The reason for this variance in this study is unknown. Could it be real? Surely, but the dramatic difference in outcomes (36% mortality in the restrictive group versus only 20% in the liberal group) seems literally hard to believe. As to what might explain this difference, if it is an artifact of some sort, it's hard to know. These results are are completely at odds with those of the much larger FOCUS randomized trial in older high-risk patients with hip fracture, in which the overall mortality rate was slightly higher (7.6% vs. 6.6%) in the liberal group, and dramatically lower overall than in this study. What caused this strikingly high mortality rate overall, and the inexplicable increased mortality in those patients treated with a restrictive trigger that is at the level of the liberal trigger in all other studies is unknown. Suffice to say, I would not apply these results to patients until they are confirmed in a second study.
Neil Blumberg MD
Vice-Chair for Laboratory Medicine
Professor of Pathology & Laboratory Medicine
Director, Transfusion Medicine/Blood Bank
Director, Clinical Laboratories
University of Rochester Medical Center
601 Elmwood Avenue
Rochester, NY 14642 (USA)