Initial Red Cell Infusion Rate and Escalation of Respiratory Support in Critically Ill Adults: A Target Trial Emulation

Background/Objectives: Current transfusion guidelines address when red cells should be given, not how fast. We estimated the association between the initial infusion rate of a first red cell transfusion and escalation of respiratory support in critically ill adults. Methods: We emulated a target trial in MIMIC-IV v3.1. Of 2790 eligible adults, 1787 received a slower (50–175 mL/h) and 1003 a faster (>175–350 mL/h) initial rate; the primary outcome was escalation to advanced respiratory support or death within 12 h. Overlap weighting estimated marginal risk differences in the overlap population, with 2000 bootstrap resamples refitting the propensity-score model. Sensitivity and continuous dose–response analyses were pre-specified. Results: The primary outcome was classifiable in 2671 patients, with 143 events. Weighted 12 h risks were 4.95% and 6.60%: risk difference 1.65 percentage points (95% CI −0.41 to 3.74), risk ratio 1.33 (0.93 to 1.92). Invasive mechanical ventilation or death, a nested key secondary outcome unadjusted for multiplicity, gave 2.55 percentage points (0.71 to 4.59); 28-day mortality gave −1.45 (−4.10 to 1.30). In the pre-specified dose–response analysis, standardised 12 h risk was lowest near 140 mL/h (4.27%) and rose to 8.83% (6.56 to 11.28) at 350 mL/h. Conclusions: The primary analysis did not distinguish the two initial-rate strategies, although the interval remained compatible with a clinically important increase in risk. The secondary and dose–response findings are hypothesis-generating and do not support changing current infusion-rate practice. These estimates support the design and sample-size planning of a prospective trial assigning infusion rate.