Transfusion Threshold Trials: The Need to Establish a Clear Difference in Transfusion Practice between Study Groups.

9.0 g/dl, patients were transfused on average at 6.8 and 7.9 g/dl, respectively, and all 13 protocol deviations in the liberal group occurred when patients with a hemoglobin less than 9.0 g/dl were not transfused (compared to all 7 deviations in the restrictive group occurring when transfusions were given to patients with hemoglobin greater than 7.0 g/dl). Patients in the liberal group received a median of 2 units during their ICU admission compared with 1 unit in the restrictive group (P = 0.17). There is a lack of clear separation in the hemoglobin levels between the two groups compared with previous large multicenter transfusion threshold trials.3,5 The median duration for which patients remained in their randomized group (i.e., the length of ICU stay) was only 4 days compared with 11 days in the TRICC trial and until discharge or death in the Villanueva and FOCUS trials. In this study, the small difference in hemoglobin concentration between the groups only emerges at 4 days. Furthermore, it is difficult to attribute such differences in outcomes to whether patients did or did not receive an average of one extra unit of blood. Taking all of these factors together, we feel it is doubtful whether the differences in outcomes can be attributed to differences in transfusion alone. The results of this study are in stark contrast to other transfusion threshold studies that have supported the safety of restrictive strategies in patients with septic shock, upper gastrointestinal bleeding, following hip and cardiac surgery and during ICU admission, and even in those with cardiovascular comorbidities. The authors postulate that inclusion of both elective and emergency surgical patients may explain some of the differences between this and other trials, but the pivotal TRICC study similarly included elective and emergency admissions to the ICU,1 and Villanueva et al.4 and Holst et al.5 report emergency admissions. Leukocytereduced blood, as used in this study, may negate some of the risks of transfusion associated with liberal strategies identified in the TRICC and TRACS studies but not in the more recent Villanueva et al.4 and TRISS studies that used leukocyte-reduced components. The FOCUS, TRISS, and Villanueva studies included patients with cancer although no subgroup analysis on these patients is currently available. The authors go on to suggest that cancer patients may be more susceptible to impaired tissue oxygenation and that impaired microvascular flow below a hemoglobin concentration of 8.0 g/dl may be associated with postoperative complications in abdominal surgery. They also refer to a Korean propensity-matched study suggesting that transfused patients with septic shock have better outcomes8; this was not corroborated by the recent randomized controlled TRISS trial. We note a small excess in major operations such as esophagectomy and gastroduodenopancreatectomy, as compared to cystectomy and hysterectomy, in the restrictive group. This may explain the excess of abdominal sepsis in this group as well as their excess mortality and increase in the composite 30-day outcome. There was also a small (albeit Transfusion Threshold Trials: The Need to Establish a Clear Difference in Transfusion Practice between Study Groups