I believe that no one would argue with the assertion that medical knowledge has dramatically increased over the past several decades and that these advances have improved our ability to care for a variety of illnesses. These advances have taken the form of new drugs, new technology, and newer ways to use “older” knowledge. However, the availability of new knowledge does not always translate to its use as many physicians have a healthy skepticism on how, or more appropriately when, to employ new knowledge (1). Studies by implementation scientists have identified various barriers and facilitators affecting the rate and pace of implementation of new medical practices (2–5). While the barriers take many forms, such as institutional inertia, unavailability of required technology, or insufficient resources, an inherent reluctance of physicians to move out of their comfort level may play a major role (1). This reluctance may persist even when application of a “new” technology, or therapy, widely accepted in one patient population is being extended to other, similar but not identical, populations.
In this issue of Pediatric Critical Care Medicine, Steffen et al (6) investigate the effect implementation of a restricted RBC transfusion practice has on the development of new or progressive multiple organ system dysfunction (NPMODS) in hemodynamically stable, critically ill children without heart disease. Patients included in the study by Steffen et al (6) represent a subset of patients included in the larger Age of Blood in Children in the PICU (ABC-PICU) study (7) in which the effect of RBC unit storage duration on outcome was evaluated; a total of 687 pediatric patients meeting inclusion criteria were included in this ad hoc secondary analysis. While the patient population and the endpoint for the study by Steffen et al (6) were similar to those in the 2007 Transfusion Requirements in the PICU (TRIPICU) study by Lacroix et al (8), demonstrating the lack of harm of a lower hemoglobin threshold for RBC transfusion (7), the patient groups in the study by Steffen et al (6) were determined based on two characteristics: the age of transfused RBCs and the hemoglobin at time of RBC transfusion (i.e., hemoglobin < 7 g/dL vs > 9.5 g/dL). However, while included patients were randomized for age of transfused RBCs in the larger ABC-PICU study, they were not randomized for transfusion threshold in this secondary analysis. Forty-nine percent of included patients experienced a “non-compliant” transfusion (i.e., hemoglobin > 7.0 g/dL at initial transfusion), with a statistically significant separation in hemoglobin levels between the two cohorts of patients (“compliant” group mean 6.5 g/dL [interquartile range (IQR) 6.2–6.8 g/dL] vs “non-compliant” group mean 7.5 g/dL [IQR, 7.2–8.0 g/dL]). Other confounding factors were not different between the groups. The authors demonstrated no difference in the occurrence rate of NPMODS, number of transfusions or relative risk of ICU- or 28-day mortality between the two transfusion groups. However, ICU-free and ventilator-free days were greater in the “compliant transfusion” group with consequent reduction in total PICU costs, including physician fees, by $38,845 (95% CI, $65,048–$12,641).
None of these findings are particularly surprising, but they do reinforce the conclusions of the larger ABC-PICU study and those of other smaller studies indicating, to the best of our ability to determine, that storage duration (i.e., “age”) of red cell units at the time of transfusion does not appear to affect clinical outcome. However, whether transfusion of stored RBCs (of any age) results in an immediate increase in oxygen delivery to tissues remains an open question. With the finding of shorter duration and/or intensity of PICU support, it is also not surprising that overall hospital costs are reduced. What is, or should be, surprising is that so many of the initial transfusions were administered above the current recommended threshold of 7.0 g/dL. While this finding may cause one to ask why there has not been better compliance with evidence based RBC transfusion guidelines 7+ years after publication of what many believe to be strong support of the safety of a restricted transfusion policy (remember, the ABC-PICU patients were recruited 7–11 yr after publication of the TRIPICU study), the relatively small deviation from the recommended threshold (7.5 g/dL observed vs recommended 7.0 g/dL) represents real progress. However, one must ask that if clinicians were no longer transfusing RBCs when the hemoglobin was in the 9–10 g/dL range, which had been accepted practice prior to the publication of the TRIPICU study, what drove the decision to transfuse at a hemoglobin of 7.5 g/dL? Was this decision driven by ongoing events such as bleeding, or was it made in anticipation that the hemoglobin might fall lower? While the presented data do not allow us to discern the answer, asking “why” may be just as important as knowing “why.” Research has identified many factors that can either hinder or facilitate adoption of new medical practices (2–5). An innate desire not to harm patients is often cited as reason for delayed adoption of new medical knowledge, a factor that may be of greater concern when the proposed change in practice involves a decrease in intensity of therapy or testing (9). The current recommendations for blood transfusion (i.e., transfusion of red cells, platelets, and/or plasma) in critically ill children represent this type of practice change (10,11). While individual physicians, or groups of physicians, may not have final authority on how much, or in what way, resources are to be allocated regarding transfusion decisions, there are physician-dependent and physician-directed strategies that have been shown to be effective measures to facilitate implementation of new transfusion practices. These include the active support for new transfusion guidelines by respected peers within the practitioner’s local medical community (i.e., practice “champions”) who can provide practitioners with outcome measures supporting the benefit of the new practice guidelines and incorporate discussion of these new transfusion guidelines into daily workflow (4,12). Additionally, electronic decision support provided in real time upon placement of a transfusion order (5,13,14) or via a smart phone app taking advantage of the ubiquity of smart phone use by clinicians (15), have also been shown to be effective in modifying transfusion practices.
While it may be human nature to be impatient and consequently to prefer being the hare, being the tortoise may suffice if we continue to ask the right questions that keep us moving on the path forward. Steffen et al (6) have asked the/a right question and in doing so they have shown us to be on the right path regarding limiting RBC transfusions in critically ill children without increasing harm.
1. Sellke F: Advancement of medical knowledge: Lessons learned from the past. Circulation 2012; 126(Suppl 21):A615
2. Wild H, Mock C, Lim A: Implementation of the WHO Trauma Care Checklist: A qualitative analysis of facilitators and barriers to use. Int J Surg 2020; 83:15–23
3. Wang Q, Zhu Y, Xie S, et al.: Facilitators, barriers and strategies for health-system guidance implementation: A critical interpretive synthesis protocol. Health Res Policy Syst 2022; 20:105
4. Donohue JM, Guclu H, Gellad WF, et al.: Influence of peer networks on physician adoption of new drugs. PLoS One 2018; 13:e0204826
5. Morris AH, Horvat C, Stagg B, et al.: Computer clinical decision support that automates personalized clinical care: A challenging but needed healthcare delivery strategy. J Am Med Inform Assoc 2022; 19:ocac143
6. Steffen KM, Tucci M, Doctor A, et al.; Pediatric Critical Care Blood Research Network (BloodNet) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network: The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial. Pediatr Crit Care Med 2023; 24:84–92
7. Spinella PC, Tucci M, Fergusson DA, et al.; ABC-PICU Investigators, the Canadian Critical Care Trials Group, the Pediatric Acute Lung Injury and Sepsis Investigators Network, the BloodNet Pediatric Critical Care Blood Research Network, and the Groupe Francophone de Réanimation et Urgences PABC-PICU Investigators, the Canadian Critical Care Trials Group, the Pediatric Acute Lung Injury and Sepsis Investigators Network, the BloodNet Pediatric Critical Care Blood Research Network, and the Groupe Francophone de Réanimation et Urgences P: Effect of fresh vs standard-issue red blood cell transfusions on multiple organ dysfunction syndrome in critically ill pediatric patients: A randomized clinical trial. JAMA 2019; 322:2179–2190
8. Lacroix J, Hébert PC, Hutchison JS, et al.; TRIPICU Investigators: TRIPICU Investigators; Canadian Critical Care Trials Group; Pediatric Acute Lung Injury and Sepsis Investigators Network: Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007; 356:1609–1619
9. Hoffman JR, Kanzaria HK: Intolerance of error and culture of blame drive medical excess. BMJ 2014; 349:g5702
10. Valentine SL, Bembea MM, Muszynski JA, et al.: Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI); Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Consensus recommendations for RBC transfusion practice in critically ill children from the pediatric critical care transfusion and anemia expertise initiative. Pediatr Crit Care Med 2018; 19:884–898
11. Nellis ME, Karam O, Valentine S, et al.; Pediatric Critical Care Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Executive summary of recommendations and expert consensus for plasma and platelet transfusion practice in critically ill children: From the Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB). Pediatr Crit Care Med 2022; 23:34–51
12. Steffen KM, Spinella PC, Holdsworth LM, et al.: Factors influencing implementation of blood transfusion recommendations in pediatric critical care units. Front Pediatr 2021; 9:800461
13. Smith M, Triulzi DJ, Yazer MH, et al.: Implementation of a simple electronic transfusion alert system decreases inappropriate ordering of packed red blood cells and plasma in a multi-hospital health care system. Transfus Apher Sci 2014; 51:53–58
14. Hibbs SP, Nielsen ND, Brunskill S, et al.: The impact of electronic decision support on transfusion practice: A systematic review. Transfus Med Rev 2015; 29:14–23
15. Dhesi AS, Wyatt JC, Estcourt LJ, et al.: Insights from developing and evaluating the NHS blood choices transfusion app to support junior and middle-grade doctor decision making against guidelines. Transfus Med 2022; 32:318–326