Red Blood Cell Transfusion at a Hemoglobin Threshold of 7 g/dl in Critically Ill Patients: A Regression Discontinuity Study

Abstract

Rationale: In critically ill patients, a hemoglobin transfusion threshold of <7.0 g/dl compared with <10.0 g/dl improves organ dysfunction. However, it is unclear if transfusion at a hemoglobin of <7.0 g/dl is superior to no transfusion. Objectives: To compare degrees of organ dysfunction between transfusion and no transfusion at a hemoglobin threshold of <7.0 g/dl among critically ill patients using quasiexperimental regression discontinuity methods. Methods: We performed regression discontinuity analysis using hemoglobin measurements from patients admitted to intensive care units in three cohorts (Medical Information Mart for Intensive Care IV, eICU, and Premier Inc.), estimating the change in organ dysfunction (modified sequential organ failure assessment score) in the 24- to 72-hour window following each hemoglobin measurement. We compared hemoglobin concentrations just above and below 7.0 g/dl using a "fuzzy" discontinuity approach, based on the concept that measurement noise pseudorandomizes similar hemoglobin concentrations on either side of the transfusion threshold. Results: A total of 11,181, 13,664, and 167,142 patients were included in the Medical Information Mart for Intensive Care IV (MIMIC-IV), eICU, and Premier Inc. cohorts, respectively. Patient characteristics below the threshold did not differ from those above the threshold, except that crossing below the threshold resulted in a >20% absolute increase in transfusion rates in all three cohorts. Transfusion was associated with increases in hemoglobin concentration in the subsequent 24-72 hours (MIMIC-IV, 2.4 [95% confidence interval (CI), 1.1 to 3.6] g/dl; eICU, 0.7 [95% CI, 0.3 to 1.2] g/dl; Premier Inc., 1.9 [95% CI, 1.5 to 2.2] g/dl) but not with improvement in organ dysfunction (MIMIC-IV, 4.6 [95% CI, -1.2 to 10] points; eICU, 4.4 [95% CI, 0.9 to 7.8] points; Premier Inc., 1.1 [95% CI, -0.2 to 2.3] points) compared with no transfusion. Conclusions: Transfusion was not associated with improved organ dysfunction compared with no transfusion at a hemoglobin threshold of 7.0 g/dl, suggesting that evaluation of transfusion targets other than a hemoglobin threshold of 7.0 g/dl may be warranted.

Keywords: anemia; blood transfusion; critical illness; hemoglobin.

Figure 1.

Exposure and outcome discontinuity at the hemoglobin threshold. Shown are estimates of the discontinuity in blood transfusion and the primary outcomes at the hemoglobin threshold of 7 g/dl. A, C, and E show discontinuity in the proportion of blood transfusions administered at the hemoglobin threshold in the MIMIC-IV, eICU, and Premier Inc. cohorts, respectively. B, D, and F show discontinuity in the modified SOFA score primary outcome at the hemoglobin threshold in the MIMIC-IV, eICU, and Premier Inc. cohorts, respectively. Solid blue dots correspond to binned hemoglobin concentrations at intervals of 0.1 g/dl. Gray areas correspond to the optimal bandwidth selected by the data-driven procedure for the local linear regression. Red lines correspond to local linear regression lines fitted to the binned hemoglobin concentrations below and above the hemoglobin transfusion threshold. MIMIC-IV = Medical Information Mart for Intensive Care IV; RBC = red blood cell; SOFA = sequential organ failure assessment.