IV iron improved postsurgical anemia in RCT
A multipronged intervention improved hemoglobin after discharge. What about life generally?
Anemia is the norm in critically ill patients. Over the past 25 years, critical care has shifted from a normalization heuristic to a restrictive, anemia-tolerant approach to transfusion. Hemoglobin levels less than 8 g/dL are common and usually left alone.
There’s good evidence this approach doesn’t increase mortality:
Guidelines on Red Cell Transfusion (Review)
Anemia is the norm among critically ill patients, who were historically transfused to normal or near-normal hemoglobin levels in the hope of optimizing their physiology and chances for recovery.
But much less is known about how severe anemia may impact long-term functional recovery after critical illness.
Most patients with ICU stays are anemic for months afterward. Lower hemoglobin levels mean lower peak exercise capacity, but it’s unclear whether that also reduces functional capacity or quality of life for most people.
Surgical patients ill enough to require ICU admission have frequently experienced significant anemia from acute blood loss. The hypothesis that mitigating their postoperative anemia might improve outcomes was recently put to the test.
Postsurgical Anemia in the ICU: A Pragmatic RCT
Warner et al (JAMA 2025) randomized 100 critically ill adults with hemoglobin <10 g/dL at the Mayo Clinic in 2022 and 2023 to receive either standard care or an intervention bundle, which included:
A dedicated phlebotomy team performed all blood draws, drawing only the smallest volume of blood necessary (using standard tubes, not pediatric tubes).
They employed a closed-loop phlebotomy system, reducing waste (a certain volume of blood is usually discarded to clear the line before blood draws).
Labs were bundled together whenever possible.
Electronic clinician-decision prompts urged clinicians to reconsider the need for repetitive laboratory assessments.
Intravenous iron supplementation when appropriate. Erythropoietin was in the protocol, but never needed (because patients responded to iron).
The small sample was mostly post-surgical patients, and most were managed in a surgical ICU.
The phlebotomy optimization reduced the number of blood draws by about 30%, and markedly reduced the total volume of blood drawn per patient from a median 142 mL in the standard group to 32 mL in the intervention arm (a 77% decrease in blood volume).
At hospital discharge, there was only a trivial increase in hemoglobin in the intervention group; both were close to 9 g/ dL.
One month after hospital discharge, however, patients in the intervention group had significantly higher hemoglobin concentrations, by +0.7 g/dL (median 12.2 g/dL vs. 11.5 g/dL in the usual care group). At three months, the elevation remained (reduced to +0.6 g/dL).
After discharge, only one patient in the intervention group received a red cell transfusion, compared to six in the standard care group.
This was a pragmatic, unblinded trial, and some crossover did occur as expected (e.g., 12% of patients in the standard care group received off-protocol IV iron later in the hospitalization), but this would not have biased the trial toward a positive result.
There were no statistically significant differences in functional outcomes, but the nominal values were worth noticing.
After discharge, patients receiving the anemia mitigation interventions reported greater quality of life, lower fatigue, depression and anxiety scores, and had higher six-minute walk distances (1211 vs. 1080 feet). The nominal increase in the intervention arm was preserved at 3 months.
As hemoglobin values were almost identical at the time of hospital discharge, it seems likely that IV iron, rather than the diminished number and volume of blood draws, was responsible for the increase in hemoglobin post-discharge in the intervention group.
“Iron Responsiveness” (Who Got IV Iron?)
In this trial, intravenous iron was given to virtually all patients classified as likely to be “iron responsive”, with either:
major bleeding during surgery (e.g., >500 mL, hemoglobin decline of >2 g/dL, or hemorrhage control surgery),
a ferritin level <100 ng/mL, or
transferrin saturation less than 20% prior to randomization.
Importantly, this applied to all patients! Virtually all the patients in the intervention arm received IV iron.
The iron preparation was not specified in the trial manuscript. Various preparations are used for this purpose, e.g., ferric carboxymaltose can be given as 1,000 mg in a single infusion.
Is This Applicable to MICU Patients?
Medical ICU patients are commonly iron-deficient, but their anemia is more often predominantly due to pre-existing chronic illness, ongoing inflammation, and impaired erythropoiesis. As such, IV iron would be expected to be less likely to provide the degree of benefit it seemed to in these post-surgical patients.
On the other hand, MICU patients tend to have longer stays, more blood draws, with a significant increase in total blood volume drawn over time as compared to surgical ICU patients. Reducing the enormous cumulative waste in blood should be a priority, as we reviewed here:
Smaller blood-collection tubes to reduce red blood cell transfusion (STRATUS trial)
Cumulatively, daily labs on hospitalized patients deplete substantial volumes of blood, almost all of which is wasted. The 4 to 6 mL of blood drawn per standard tube is a legacy of older equipment: modern testing machines only need <0.5 mL per sample, and the rest is discarded. More blood is drawn and discarded the next day, and the next, and the next—w…
Conclusions
As part of a multifaceted intervention to optimize and limit phlebotomy in surgical patients, intravenous iron seemed to lead to a delayed but sustained increase in hemoglobin after hospital discharge.
Functional outcomes may have also improved, but the study was too small to tell.
This was also a single-center, unblinded, pragmatic trial. Although the postdischarge hemoglobin levels are fairly impervious to bias, subjective functional outcomes are not.
The findings may not be directly applicable to medical ICU patients, whose anemia is less likely to respond to IV iron.
Improvements in hemoglobin are great, and avoiding preventable transfusions is even better. But does an increase in hemoglobin lead to improvement in meaningful outcomes like functional capacity and quality of life?
More than 20 randomized trials are in process or recently completed, testing IV iron as a treatment for postsurgical anemia.
One trial is in process (n=514) in colorectal surgery patients, testing whether IV iron reduces blood transfusions.
Another (n~310) will test IV iron’s effects on disability in elderly patients after cardiac surgery.
Enrollment for the others is between 20 and 200 patients each, probably making them inadequately powered to provide convincing answers to these questions.
This is such a small, controlled study population that it’s hard to make any conclusions about ICU patients in general.