Practical Anemia Bundle and Hemoglobin Recovery in Critical Illness: A Randomized Clinical Trial

Abstract

Importance: Anemia is a common complication of surgery and acute illness that is associated with adverse clinical outcomes. The role of anemia prevention and treatment strategies in this setting remains unclear.

Objective: To evaluate the effect of a multifaceted anemia management bundle vs standard care on posthospitalization hemoglobin recovery and multidimensional functional outcomes in survivors of acute illness.

Design, setting, and participants: This parallel group randomized clinical trial, known as the Practical Anemia Bundle for Sustained Blood Recovery, was conducted at postsurgical and medical intensive care units at a large US medical center. Critically ill patients (aged ≥18 years) with moderate to severe anemia (hemoglobin concentration <10 g/dL) were enrolled between March 2022 and November 2023. Participants were randomly assigned 1:1 to the intervention or standard care group. Intention-to-treat analyses were performed between July 2024 and January 2025.

Intervention: The intervention bundle was delivered throughout the duration of hospitalization and included optimized phlebotomy practices, clinical decision support, and pharmacological anemia treatment with intravenous iron.

Main outcomes and measures: The primary outcome was the mean difference in hemoglobin concentration at 1 month after hospital discharge.

Results: A total of 100 patients (median [IQR] age, 68 [61-72] years; 57 men [57.0%]; 65 [65.0%] with postsurgical admission to the intensive care unit) were enrolled during acute illness. Forty-nine patients (49.0%) were assigned to receive the intervention, and 51 (51.0%) were assigned to receive standard care. Hemoglobin concentration at 1 month after discharge was greater in patients receiving the intervention vs standard care (median [IQR], 12.2 [11.8-13.0] g/dL vs 11.5 [10.2-12.6] g/dL; adjusted mean difference, 0.69 [95% CI, 0.13-1.20] g/dL; P = .02).

Conclusions and relevance: This randomized clinical trial found that a multifaceted anemia prevention and treatment bundle was feasible, was well tolerated, and improved posthospitalization hemoglobin concentrations up to 3 months in critically ill adults. These findings can inform the design of future trials.

Trial registration: ClinicalTrials.gov Identifier: NCT05167734.

Figure 1.. Study Flow Diagram

Patients were enrolled during their index intensive care unit (ICU) admission. Those who were not enrolled during index ICU admission but were subsequently readmitted to the ICU during the index hospitalization were not eligible for enrollment. AMI indicates acute myocardial infarction; IV, intravenous.

Figure 2.. Hemoglobin Concentrations Over Time, With Primary Outcome Mean Difference at the 1-Month Follow-Up

There were 26, 0, 12, and 15 participants missing intensive care unit (ICU) discharge, hospital discharge, 1-month follow-up, and 3-month follow-up hemoglobin values, respectively. Estimates were calculated using a linear mixed-effects model adjusted for baseline hemoglobin concentration, age, sex, and surgical vs medical ICU admission type. Estimates show the intervention-associated increase in hemoglobin concentration (to convert g/dL to g/L, multiply by 10.0) at a given time point.

Figure 3.. Multidimensional Functional Outcomes Up to 3 Months After Hospitalization

Estimates were calculated using linear or generalized linear mixed-effects models. All estimates are odds ratios (ORs) and correspond to the intervention-associated multiplicative increase in odds of a higher score or odds for the given event. Quality of life and fatigue and physical function outcomes were also adjusted for baseline Katz Index of Independence in Activities of Daily Living (Katz-ADL; score range: 0-6, with higher scores indicating better physical function). 6MWD indicates 6-minute walk distance (greater distance walked indicates greater ambulatory capacity); EQ-VAS, EuroQol Visual Analogue Scale (score range: 0-100, with higher scores indicating better quality of life); FACIT, Fatigue Subscale, Functional Assessment of Chronic Illness Therapy (inverted score range: 0-52, with higher scores indicating less fatigue); HADS, Hospital Anxiety and Depression Scale (score range: 0-21, with higher scores indicating greater symptom burden); IES-R, Impact of Events Scale–Revised (score range: 0-88, with higher scores indicating greater symptom burden); and MoCA-Blind, Montreal Cognitive Assessment, Blind (score range: 0-22, with higher scores indicating better cognition).