A retrospective observational analysis of red blood cell transfusion practices in stable, non-bleeding adult patients admitted to nine medical-surgical intensive care units

The need to address medical overuse, defined as “the provision of medical services for which the potential for harm exceeds the potential for benefit” [1], is increasingly being recognized by healthcare systems internationally [2–5]. In 2012, the Joint Commission on medical overuse in the USA identified a list of the top five overused medical procedures based on available evidence and expert-recommended standards of appropriateness [6]; among those listed was the over-transfusion of blood and blood products, such as red blood cells (RBCs).

Allogeneic RBC transfusion is a common procedure for many medical and surgical specialties and is typically used to manage hemorrhagic or anemic events among hospitalized patients [7–11]. However, with the risks of infection or even mortality associated with RBC transfusions, overuse is of significant concern for patient safety and quality of care [12, 13]. Beyond this, blood products are costly resources and are limited in their availability; current estimates suggest that acquisition and administration costs for RBC transfusions range internationally from $500 to $1200 USD per RBC unit transfused [14]. Blood conservation is, therefore, additionally important to maintaining financial stewardship in healthcare systems worldwide.

To guide appropriate use of RBC transfusion, clinical guidelines such as those from the AABB (formerly the American Association of Blood Banks) [15] have developed evidence-based recommendations predicated on set pre-transfusion hemoglobin concentration values. For example, for most stable, non-bleeding hospitalized patients, including those admitted to the intensive care unit (ICU), RBC transfusions are not recommended above a hemoglobin level of 70 g/L [15]. Informing such recommendations are a number of randomized controlled trials (RCTs) that have examined the efficacy of a restrictive (e.g., hemoglobin value of 70 g/L) versus a liberal transfusion strategy (e.g., hemoglobin value of 100 g/L). [16–20]. A recent systematic review of 31 RCTs found that, with the exception of certain high-risk groups (i.e., neurological injury or disorders, acute coronary syndrome), a restrictive transfusion strategy decreased transfusion requirements without increasing the risk of mortality and adverse outcomes for most hospitalized patients [21].

Given this established evidence base, the primary objective of this retrospective observational study was to measure the utilization and costs of RBC transfusion practices among medical-surgical ICUs and to compare this information to recommended best practice.

In this multi-center, retrospective observational study, the RBC transfusion practices in nine adult medical-surgical ICUs were examined. We identified a total of 4632 unique RBC transfusions events in 2287 mixed medical and surgical ICU admissions. Patients within this cohort received approximately two transfusions per ICU admission, with 1 RBC unit transfused per event, and had a mean pre-transfusion hemoglobin level of 73.4 g/L. Among 4487 RBC transfusion events, 61% were associated with a pre-transfusion hemoglobin value at or above 70 g/L. Over the 33-month study period, this was estimated to cost over $1.8M CAD to the healthcare system. Factors such as being male, 75 years of age or older, admission to the ICU from the operating room, and an ICU admission diagnosis of gastrointestinal bleeding or trauma were positively associated with RBC transfusions events with a hemoglobin value greater or equal to 70 g/L. Moreover, having a pre-transfusion hemoglobin value at or above 70 g/L was also associated with an increase in ICU mortality. There was no impact on overall hospital mortality.

We specifically sought to examine RBC transfusions among critically ill patients for whom a restrictive transfusion strategy is supported by the most current, high-quality evidence [16–21]. In doing so, we acknowledged that a restrictive pre-transfusion hemoglobin threshold will not apply in all clinical situations. For instance, in some hemorrhagic or ischemic events, clinical judgment should subvert laboratory value-based thresholds. To account for such reasonable clinical exclusions, we excluded from analysis a considerable number of patients (i.e., greater than 50% of ICU admissions with a RBC transfusion event) for whom a restrictive transfusion strategy has not been proven safe, nor superior, to a liberal transfusion strategy (e.g., chronic anemia, active blood loss, acute coronary syndrome, myocardial infarction, and neurological or traumatic brain injury) [21]. With our final cohort, we, therefore, aimed to decrease the potential for misclassifying a RBC transfusion event—for which a restrictive transfusion approach would not be appropriate—and allowed a conservative evaluation of RBC transfusion practices in the ICU.

Reduced exposure to RBCs, through the adoption of a restrictive pre-transfusion hemoglobin threshold (i.e., less than 70 g/L), has been increasingly recognized in transfusion guidelines as the best practice for most stable, non-bleeding adult patients in the ICU [7, 15, 27, 28]. Within our cohort, we found that over half of all examined RBC transfusions may have occurred outside of the recommended best practice. While these findings suggest potential over-transfusion in the ICU, there have been minor improvements in transfusion practices over time. The reason for this is unknown but is likely the result of increasing awareness and attention to the subject. We also found that over 40% of RBC transfusions examined in our study were associated with a pre-transfusion hemoglobin value between 70 g/L and 79 g/L. Visual inspection of the stratified patient characteristics (Additional file 2) did not suggest differences between transfusions associated with a hemoglobin value below 70 g/L and 70–79 g/L. Interestingly, previous qualitative studies that have examined factors influencing physician transfusion behaviors found the greatest uncertainty among physicians when deciding whether to transfuse patients with a hemoglobin level within this borderline range [29, 30]. Such uncertainty may similarly be reflected in our findings, and targeted efforts to better inform physician decision-making for transfusing such patients may be warranted.

Similar studies examining the appropriateness of RBC transfusion practices have been described in the literature. Previous retrospective audits, for example, have primarily focused on characterizing mean pre-transfusion hemoglobin levels and found them to range substantially between 71 g/L and 91 g/L for most non-hemorrhagic, ICU patient populations [31–34]. One of the larger studies conducted in the USA, a longitudinal analysis RBC transfusion practice between 1997 and 2007, reported a similar mean pre-transfusion hemoglobin level to our patient cohort after their 10 year follow-up period (significantly decreasing from 79 ± 1.3 to 73 ± 1.3 g/L) [32]. In addition, Netzer et al. [32] observed a significant decrease in the proportion of patients who were transfused at a hemoglobin level of less than 70 g/L. In contrast, studies that have examined average transfusion volumes have reported higher numbers of RBC units per transfusion event compared to our study results, ranging from 2 to 4.3 RBC units [32, 35]. While it is difficult to reconcile specific reasons for observed differences between these previous studies and our present findings, some differences are likely attributable to variations in the patient case-mix, ICU structure or culture, or even the time since the publication (and acceptance) of seminal and relevant literature and guidelines.

We conducted additional analytical investigations that represent novel contributions to the existing literature and offer considerations for policy and practice, as well as future research. The costing analysis, for instance, enabled the valuation of not only RBC transfusions across the ICUs, but also of the opportunity cost of potentially inappropriate practices over the 33-month study period. Presenting such costing outcomes provides another perspective for clinical experts to reflect on as the stewards of healthcare resources. This information can also help healthcare system decision-makers implement interventions whose implementation costs could still yield a reasonable return on investment and, as such, improve the overall efficiency of care delivered.

We also identified several factors associated with RBC transfusions with a hemoglobin level above 70 g/L. In particular, ICU admission diagnoses of gastrointestinal bleeding and trauma were associated with at least a 30–50% increase in the odds of these transfusions. Despite the evidence supporting the use of a restrictive RBC transfusion strategy for both of these patient groups [21], as well as our exclusion of transfusions among patients with active bleeding, the propensity for hemorrhagic outcomes with such conditions may account for the increased odds in the observed cases [36, 37]. Due to the overlap in 95% confidence intervals across point estimates, we did not find any one (or few) factor(s) that markedly increased the odds of transfusion over other factors. This suggests that there may be several drivers, both characterized and uncharacterized (e.g., level of physician experience, cultural influences) in our present work that act in concert and underlie the observed proportion of overuse.

In addition, the downstream impacts of pre-transfusion hemoglobin values in our transfused patient cohort differed by ICU and hospital. With respect to mortality, we found that the odds in the ICU were increased for transfused patients with a pre-transfusion hemoglobin of 70 g/L or more, but there was no difference in hospital deaths. Previous meta-analyses of RCTs comparing restrictive versus liberal hemoglobin thresholds found that there was no difference in ICU mortality between groups, yet the risk ratio for hospital mortality was lower among those randomized to the restrictive threshold [21]. While these differences in mortality outcomes may be due to unmeasured confounding in our observational data, our present findings still do not indicate an increased risk of harm for transfused patients with a lower pre-transfusion hemoglobin value (i.e., below 70 g/L).

The present study examined the utilization and costs of RBC transfusion practices within nine medical-surgical ICUs and identified that more than half are still provided above guideline-recommended pre-transfusion hemoglobin thresholds. There is still a large opportunity for improvement in RBC transfusion practices from a patient safety, quality, and financial perspective. Future work to fully characterize the rationale for transfusion decisions as well as understand the factors that underlie the behavior, whether at the environmental or individual physician level, may aid in developing targeted interventions to eliminate overuse [29, 30]. Importantly, the lessons learned from the present study may also help to inform larger-scale blood management programs beyond critical care [38]. With increasing pressures faced by healthcare systems globally to improve quality of care in light of scarce resources, such efforts to address medical overuse are of increasing necessity.