By Samuel Nadler, MD, PhD

Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle

Dr. Nadler reports no financial relationships relevant to this field of study.

SYNOPSIS: In patients at moderate to high risk of complications with cardiac surgery, a transfusion threshold of hemoglobin < 7.5 g/dL showed similar outcomes to a threshold of < 9.5 g/dL.

SOURCE: Mazer CD, Whitlock RP, Fergusson DA, et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med 2017;337:2133-2144.

Since the original Transfusion Requirements in Critical Care (TRICC) trial published in 1999,1 there have been numerous studies demonstrating the benefits of restrictive transfusion threshold in critical care. However, there has been ongoing concern in patients with cardiovascular disease regarding whether restrictive thresholds are appropriate. In 2015, the authors of the Transfusion Indication Threshold Reduction (TITRe2) study reported that a restrictive transfusion strategy was not superior to liberal thresholds in terms of morbidity, but showed an increased 90-day mortality as a secondary outcome (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.00-2.67; P = 0.045).2

The Transfusion Requirements in Cardiac Surgery III (TRICS III) trial was a multicenter, open-label, non-inferiority trial of 5,243 adults undergoing cardiac surgery with a moderate to high risk for death as determined by elevated European System for Cardiac Operative Risk Evaluation (EuroSCORE I) data. Patients were randomized to a restrictive (transfuse for hemoglobin < 7.5 g/dL) or liberal (< 9.5 g/dL) strategy, with the primary outcome of all-cause mortality, myocardial infarction, stroke, or new-onset renal failure with dialysis. The authors powered the trial with a 90% chance to detect a non-inferiority margin of 3% risk difference (assuming a 10% event rate).

Overall, 52.3% of patients randomized to the restrictive threshold received transfusions compared with 72.6% of patients in the liberal threshold (odds ratio [OR], 0.41; 95% CI, 0.37-0.47), with a median number of units transfused of two vs. three in the restrictive and liberal thresholds, respectively. The composite primary outcome occurred in 11.4% of the restrictive arm vs. 12.5% in the liberal arm (OR, 0.90; 95% CI, 0.76-1.07). There were no differences in the individual rates of death, stroke, myocardial infarction, or renal failure. A secondary analysis demonstrated a slightly shorter ICU and hospital length of stay in the restrictive group vs. the liberal group (HR, 0.89 vs. 0.93, respectively). Furthermore, there were no significant differences in infection, bowel infarction, kidney injury, seizure, delirium, or encephalopathy.

COMMENTARY

The TRICS III study represents the strongest evidence to date that a restrictive transfusion threshold is appropriate even in patients undergoing moderate- to high-risk cardiac surgery. In contrast to the TITRe2 study, which previously raised concerns, the authors of TRICS III randomized patients preoperatively, and mortality was defined as part of the composite primary outcome. Fewer transfusions were reported both in the operating room and in the ICU.

In the restrictive group, 27.7% received transfusions intraoperatively, compared with 51.8% in the liberal arm with a rate ratio 0.36 (95% CI, 0.32-0.40). Postoperatively, 35.7% of the restrictive group and 51.6% of the liberal group received transfusions (rate ratio, 0.52; 95% CI, 0.46-0.58), although the median number of units transfused in the ICU was similar in the two groups. The median number of units transfused was only reduced from three in the liberal threshold group to two in the restrictive group, but the distribution of transfusions was informative. In the restrictive threshold group, 47.7% received no transfusions, compared with 27.4% in the liberal group. Furthermore, 22.2% of the liberal group received five or more units, compared with only 12% in the restrictive group. Thus, adopting a restrictive threshold seems to have reduced transfusions substantially without significant adverse effects.

REFERENCES

  1. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409-417.
  2. Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372:997-1008.