Lower versus higher hemoglobin threshold for transfusion in ARDS patients with and without ECMO

Abstract

Background: Efficacy and safety of different hemoglobin thresholds for transfusion of red blood cells (RBCs) in adults with an acute respiratory distress syndrome (ARDS) are unknown. We therefore assessed the effect of two transfusion thresholds on short-term outcome in patients with ARDS.

Methods: Patients who received transfusions of RBCs were identified from a cohort of 1044 ARDS patients. After propensity score matching, patients transfused at a hemoglobin concentration of 8 g/dl or less (lower-threshold) were compared to patients transfused at a hemoglobin concentration of 10 g/dl or less (higher-threshold). The primary endpoint was 28-day mortality. Secondary endpoints included ECMO-free, ventilator-free, sedation-free, and organ dysfunction-free composites.

Measurements and main results: One hundred ninety-two patients were eligible for analysis of the matched cohort. Patients in the lower-threshold group had similar baseline characteristics and hemoglobin levels at ARDS onset but received fewer RBC units and had lower hemoglobin levels compared with the higher-threshold group during the course on the ICU (9.1 [IQR, 8.7-9.7] vs. 10.4 [10-11] g/dl, P < 0.001). There was no difference in 28-day mortality between the lower-threshold group compared with the higher-threshold group (hazard ratio, 0.94 [95%-CI, 0.59-1.48], P = 0.78). Within 28 days, 36.5% (95%-CI, 27.0-46.9) of the patients in the lower-threshold group compared with 39.5% (29.9-50.1) of the patients in the higher-threshold group had died. While there were no differences in ECMO-free, sedation-free, and organ dysfunction-free composites, the chance for successful weaning from mechanical ventilation within 28 days after ARDS onset was lower in the lower-threshold group (subdistribution hazard ratio, 0.36 [95%-CI, 0.15-0.86], P = 0.02).

Conclusions: Transfusion at a hemoglobin concentration of 8 g/dl, as compared with a hemoglobin concentration of 10 g/dl, was not associated with an increase in 28-day mortality in adults with ARDS. However, a transfusion at a hemoglobin concentration of 8 g/dl was associated with a lower chance for successful weaning from the ventilator during the first 28 days after ARDS onset.

Trial registration: ClinicalTrials.gov NCT03871166.

Keywords: ARDS; Red blood cells; Transfusion.

Conflict of interest statement

The authors have no competing of interest in relation to this manuscript.

Figures

Fig. 1

Study flow diagram. Patients were grouped according to their individual hemoglobin threshold into patients transfused at a hemoglobin concentration of 8 g/dl or less (lower threshold) and patients transfused at a hemoglobin concentration of 10 g/dl or less (higher threshold)

Fig. 2

Hemoglobin concentrations and transfusion requirements between the lower-threshold group and higher-threshold group. The hemoglobin concentrations at ARDS onset (a), the number of transfused RBC units within 28 days of ARDS therapy (b), and the hemoglobin concentrations within 28 days of ARDS therapy (c) are presented. Gray boxes help to visualize the coherence of the range of individual hemoglobin thresholds that was used for grouping and the hemoglobin concentrations at admission and within 28 days of ARDS therapy. Median daily time-weighted average hemoglobin concentrations during 28 days of ARDS therapy in the lower-threshold group and higher-threshold group (d). Daily time-weighted average hemoglobin concentrations overcome the complexity that number and timing of daily blood gas samples were not exactly the same in all patients. First values were the baseline hemoglobin concentrations at onset of ARDS. Day 0 was defined as the time of ARDS onset to the end of that day. Data are shown as median and 25th and 75th percentiles

Fig. 3

Kaplan–Meier survival estimates of the mortality within 28 days after onset of ARDS between the lower-threshold group and higher-threshold group. For each curve, 95% confidence intervals (dotted lines) are shown. The hazard ratio with 95% confidence intervals are provided. The median observation time was 24 days (IQR, 13–28) in the lower-threshold group and 27 days (17–28) in the higher-threshold group. There was no difference in censoring between the two transfused groups (P = 0.30)

Fig. 4

Cumulative incidence curves of ECMO-free (a), ventilator-free (b), sedation-free (c), and organ dysfunction-free (d) days composites between the lower-threshold group and higher-threshold group. For each curve, 95% confidence intervals (dotted lines) are shown. The subdistribution hazard ratio (SHR) with 95% confidence intervals is provided. The SHR is calculated from a competing risk regression providing the chance of the lower-threshold group compared with the higher-threshold group for the particular event (ECMO removal, weaning from mechanical ventilation, RASS 0 or − 1, SOFA score < 6) accounting for the existence of the alternative outcome of death. For better interpretation, the y-axis of the ventilator-free days composite (b) is scaled from 0 to 40% instead of 0 to 100%. Definition of abbreviations: TTtransfusion threshold, ECMO extracorporeal membrane oxygenation, MV mechanical ventilation, OD organ dysfunction

Fig. 5

Subgroup analyses of failure-free composites between the lower-threshold group and higher-threshold group in the cohort of patients with ECMO (a) and the cohort of patients without ECLS (b). For each failure-free composite, the cumulative events within 28 days after ARDS onset and the appropriate effect measure (subdistribution hazard ratio [SHR]) with 95% confidence intervals is provided. The SHR has to be interpreted as a chance of the lower-threshold group compared with the higher-threshold group for reaching the particular event (ECMO removal, weaning from mechanical ventilation, stopping sedation, SOFA score < 6, stopping renal replacement therapy, stopping vasopressors) accounting for the existence of the alternative outcome of death. The subdistribution hazard ratio is presented on a log-transformed axis. Definition of abbreviations: RRT renal replacement therapy, ECMO extracorporeal membrane oxygenation, ECLS extracorporeal life support