Wednesday, March 18, 2015

Restrictive vs. liberal transfusion strategies may not matter after cardiac surgery

Restrictive transfusion thresholds after cardiac surgery didn't improve outcomes compared to liberal ones, a study found.

The Transfusion Indication Threshold Reduction (TITRe2), a multicenter, parallel-group trial, recruited patients age 16 and older undergoing nonemergency cardiac surgery at 17 British centers. Patients with a postoperative hemoglobin level of less than 9 g/dL were randomly assigned to a restrictive transfusion threshold of hemoglobin level <7.5 g/dL (n=1,000) or a liberal transfusion threshold of <9 g/dL (n=1,003). In the liberal-threshold group, patients received 1 unit of red cells immediately after randomization and received another unit if the hemoglobin level remained or dropped below 9 g/dL again. In the restrictive-threshold group, patients received 1 unit if the hemoglobin level dropped below 7.5 g/dL and another unit if the level remained or dropped below 7.5 g/dL again.

The primary outcome was a composite of a serious infection (sepsis or a wound infection) or an ischemic event such as a permanent stroke, myocardial infarction, infarction of the gut, or acute kidney injury within 3 months. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months afterward. Results appeared in the March 12 New England Journal of Medicine

Transfusion rates after randomization were 53.4% in the restrictive strategy group and 92.2% in the liberal strategy group. Primary outcomes occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% CI, 0.91 to 1.34; P=0.30). There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio=1.64; 95% CI, 1.00 to 2.67; P=0.045). The researchers noted that serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups.

The study creates new uncertainty about using a restrictive threshold for transfusion after cardiac surgery, the researchers wrote. The TITRe2 trial differs from previous observational studies of transfusion thresholds in that all the participants had cardiovascular disease and a substantial proportion of participants were likely to have been dependent on oxygen supplementation immediately after surgery. This group may have been at the limits of their cardiovascular reserve and may benefit from higher hemoglobin levels, the authors speculated. "Patients with cardiovascular disease may represent a specific high-risk group for which more liberal transfusion thresholds are to be recommended," they wrote.

The results are surprising, said an accompanying editorial. "Cardiac surgery departments should review the findings of the TITRe2 trial and decide which threshold they deem to be most appropriate for transfusion. Protocols should be developed to minimize deviation from the agreed-upon approach, and feedback should be provided to hold operators accountable to the institution's standard of care," the editorialist wrote.