More Evidence Supporting a Conservative Approach to Red Blood Cell Transfusion

Although the Transfusion Requirements in Critical Care (TRICC) trial¹ showed the benefits of a conservative transfusion strategy more than 15 years ago, many physicians remain skeptical about the safety of lower hemoglobin thresholds for red cell transfusion in critically ill patients. In particular, evidence from at least some clinical studies^2,3 has suggested that higher hemoglobin targets may be advantageous for patients with septic shock.

To better define the benefits and risks of different hemoglobin thresholds for red blood cell (RBC) transfusion, Dr. Lars Holst and colleagues conducted a multicenter, parallel-group trial that randomized intensive care unit (ICU) patients with septic shock to receive one unit of leukoreduced red cells either at a hemoglobin concentration of 9 g/dL or less (higher threshold) or at a hemoglobin concentration of 7 g/dL or less (lower threshold). The primary outcome measure was death at 90 days.

The Transfusion Requirements in Septic Shock (TRISS) trial was conducted at 32 sites in Denmark, Sweden, Norway, and Finland between December 2011 and December 2013. Randomization was stratified by study site and by the presence or absence of active hematologic cancer. More than 85 percent of screened patients were randomized; the most common reason for exclusion was prior transfusion of RBCs. Of 1,005 patients who underwent randomization, 998 (99.3%) were included in the primary outcome (mortality) analysis. The baseline clinical characteristics of the two groups were similar, including age (median age, 67 years for both groups) and severity of illness scores. Although approximately 14 percent of patients in each group had chronic cardiovascular disease, patients with acute myocardial infarction were excluded. The median number of RBC units received was less in the lower threshold group (one unit vs. four units).

Ninety days after study entry, overall mortality was 43 percent in the lower-threshold group, and 45 percent in the higher-threshold group (relative risk, 0.94; 95% CI, 0.78 to 1.09; p=0.44). Neither adjustment for baseline risk factors nor per-protocol analyses altered the findings. Secondary outcome measures included the use of life support at days 5, 14, and 28 after randomization; serious adverse reactions (including transfusion-related acute lung injury and transfusion-associated circulatory overload) while in the ICU; and cerebral, myocardial, limb, or intestinal ischemic events while in the ICU. No statistically significant difference between treatment groups was observed for any of these secondary endpoints.