IV iron may improve management of postoperative anemia

The IV infusion of ferric carboxymaltose may be preferable to observation in the management of patients with functional iron deficiency anemia after surgery, according to the results of a randomized controlled trial.

Outcome improvements among patients assigned to ferric carboxymaltose suggest that IV iron infusion should be added to patient blood management guidelines, the researchers wrote.

“Anemia in the perioperative period is associated with increased morbidity and mortality, and also adversely affects quality of life,” Alhossain A. Khalafallah, FRCAP, associate professor at University of Tasmania and physician at Launceston General Hospital in Australia, and colleagues wrote. “Furthermore, it is an independent risk factor associated with adverse postoperative outcomes, such as increased length of time spent in ICUs, longer hospital stays, and more postoperative complications.”

Observation serves as the standard of care for patients with iron deficiency anemia who undergo surgery.

Khalafallah and colleagues assessed whether IV ferric carboxymaltose could improve iron stores, hemoglobin concentrations and overall outcomes after surgery.

The researchers identified 201 people in Australia (median age, 66 years; interquartile range, 59-74) with functional iron deficiency anemia who underwent elective surgery.

The majority of patients (n = 156) underwent major orthopedic surgery. Other surgical procedures included abdominal surgery (n = 19), gynecologic surgery (n = 10), urologic surgery (n = 8) and other operations (n = 8).

Researchers randomly assigned patients to a single 1,000 mg IV dose of ferric carboxymaltose (intervention; n = 103) or standard observation (n = 98).

Changes in hemoglobin concentrations and iron store 4 weeks after surgery served as the primary endpoint. The researchers also calculated the number of transfused units of blood required until hospital discharge.

The observation group had a baseline mean hemoglobin of 105.5 g/L (standard deviation [SD], 13.8), compared with 106.2 g/L (SD, 11.9) in the intervention group.

The intervention group had a significant improvement in mean hemoglobin concentration at 4 weeks (130.1 g/L [SD, 11.3] vs. 121.5 g/L [SD, 14.5]; mean difference, 7.84; P < .0001).

Further, treatment with ferric carboxymaltose improved serum iron (5.36 mol/L; 95% CI, 3.62-7.09), iron saturation (11.40%; 95% CI, 8.33-14.50) and serum ferritin concentrations (468g/L; 95% CI, 355-582). The researchers did not observe a difference in transferrin concentrations (0.06 g/L; 95% CI, –0.97 to 1.09).

Fewer patients assigned to the intervention group required blood transfusions while hospitalized (1 vs. 5; incidence rate ratio = 0.1; 95% CI, 0.01-0.85).

Patients assigned to ferric carboxymaltose also had a shorter mean hospital stay (7.8 days vs. 11.6 days; P = .049). Two patients assigned ferric carboxymaltose and 13 patients assigned standard care experienced severe infections requiring antibiotics.

The researchers observed no adverse events or infusion reactions associated with ferric carboxymaltose.

Study limitations included the open-label design and the relatively small patient population.

“Postoperative IV ferric carboxymaltose is a safe and effective alternative to management of postoperative functional iron deficiency anemia,” Khalafallah and colleagues wrote. “Our results, together with results from other studies showing similar effectiveness with IV iron, and the substantial potential benefits and cost savings, should prompt reassessment of current blood management guidelines.”

Potential concerns remain despite the positive outcomes of this trial, Manuel Muñoz, MD, PhD, professor of perioperative transfusion medicine at University of Málaga in Spain, and Michael Auerbach, MD, professor of medicine at Georgetown University School of Medicine, wrote in an accompanying editorial.

“Although these results are reassuring, a note of caution is prudent: Phosphate plays an important role in human physiology, and hypophosphatemia is frequently observed after infusion of ferric carboxymaltose and might have clinical consequences,” Muñoz and Auerbach wrote. “Especially when severe (< 2 mg/dL), hypophosphatemia is associated with various complications, including persisting fatigue, myocardial depression, proximal myopathy and rhabdomyolysis. ... Unfortunately, phosphate concentrations were not measured in this trial.”

However, Muñoz and Auerbach suggested these study findings may represent a new standard of care.

“We are grateful for this well-conducted, statistically sound prospective trial, which elucidates another method of administering IV iron, and hope that surgeons move forward in adding this safe, effective and convenient therapy to the current treatment algorithm for postoperative anemia,” Muñoz and Auerbach wrote. “We applaud the investigators for not misrepresenting the improved safety of this IV iron formulation compared with others, and agree that patient blood management guidelines should be updated, incorporating the use of postoperative IV iron to optimize patient outcomes after elective and nonelective procedures.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures. Muñoz reports honoraria from Pharmacosmos, Sandoz, Vifor Pharma, Vifor Pharma España and Zambon. Auerbach reports honoraria from AMAG Pharmaceuticals, Luitpold Pharmaceuticals/American Regent, and Pharmacosmos.