Monday, November 06, 2017

Liberal versus restrictive transfusion strategy: the debate is not quite over

Although a hemoglobin of 7 has become a widely accepted threshold for transfusion in a variety of situations there remain areas of uncertainty. One of these areas is ischemic heart disease. The NIH sponsored MINT is being organized to address this question. (Public Citizen thinks it should not be carried out). One of the questions here is whether there is equipoise for such a trial. Public Citizen, while leveling their principal objections toward trial ethics and the informed consent process, implies that there is no equipoise and a higher hemoglobin threshold should be accepted. The argument that equipoise exists is based on the fact that for ischemic heart disease there are only low level data to guide transfusion practices. High level trials lumped patients together having many different underlying diseases. How might transfusion thresholds apply to various subgroups? That raises nearly endless questions.

What about, for example, oncology patients with septic shock? Check out the results of this single center RCT:

Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock.

Design: Single center, randomized, double-blind controlled trial.

Setting: Teaching hospital.

Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission.

Interventions: Patients were randomized to the liberal (hemoglobin threshold, less than 9 g/dL) or to the restrictive strategy (hemoglobin threshold, less than 7 g/dL) of RBC transfusion during ICU stay.

Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p less than 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03).

Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

This contributes to the evidence we have to guide transfusion practices but also serves as a reminder that there is no pat answer. Clinical judgment must surpass slavish adherence to pathways and guidelines, which is what evidence based medicine is all about.

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