title: Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness.
abstract: BACKGROUND
  Critical illness is characterized by hypoferremia, iron-deficient erythropoiesis (IDE), and anemia. The relative risks and benefits of iron supplementation in this setting are unknown.
  
  
  METHODS
  Anemic, critically ill surgical patients with an expected intensive care unit length of stay (ULOS) >or= 5 days were randomized to either enteral iron supplementation (ferrous sulfate 325 mg three times daily) or placebo until hospital discharge. Outcomes included hematocrit, iron markers (i.e., serum concentrations of iron, ferritin, and erythrocyte zinc protoporphyrin [eZPP]), red blood cell (RBC) transfusion, transfusion rate (mL RBC/study day), nosocomial infection, antibiotic days, study length of stay (LOS), ULOS, and death. Iron-deficient erythropoiesis was defined as an elevated eZPP concentration.
  
  
  RESULTS
  Two hundred patients were randomized; 97 received iron, and 103 received placebo. Socio-demographics, baseline acuity, hematocrit, and iron markers were similar in the two groups. No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days. However, patients treated with iron were significantly less likely to receive an RBC transfusion (29.9% vs. 44.7%, respectively; p = 0.03) and had a significantly lower transfusion rate (22.0 mL/day vs. 29.9 mL/day; p = 0.03). Subgroup analysis revealed that these differences were observed in patients with baseline IDE only. Iron and placebo groups did not differ with respect to incidence of infection (46.8% vs. 48.9%; p = 0.98), antibiotic days (14 vs. 16; p = 0.45), LOS (14 vs. 16 days; p = 0.24), ULOS (12 vs. 14 days; p = 0.69), or mortality rate (9.4% vs. 9.9%; p = 0.62).
  
  
  CONCLUSIONS
  Enteral iron supplementation of anemic, critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion. A trial comparing enteral and parenteral iron supplementation in this setting is warranted (ClinicalTrials.gov number, NCT00450177).
authors.affiliation: Department of Surgery, Weill Cornell Medical College, New York, New York 10021, USA. frp9005@nyp.org
authors.forename: Fredric M
authors.initials: FM
authors.lastname: Pieracci
authors.forename: Peter
authors.initials: P
authors.lastname: Henderson
authors.forename: John Rocco Macmillan
authors.initials: JR
authors.lastname: Rodney
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Holena
authors.forename: Alicia
authors.initials: A
authors.lastname: Genisca
authors.forename: Ivan
authors.initials: I
authors.lastname: Ip
authors.forename: Steven
authors.initials: S
authors.lastname: Benkert
authors.forename: Lynn J
authors.initials: LJ
authors.lastname: Hydo
authors.forename: Soumitra R
authors.initials: SR
authors.lastname: Eachempati
authors.forename: Jian
authors.initials: J
authors.lastname: Shou
authors.forename: Philip S
authors.initials: PS
authors.lastname: Barie
mesh_terms: D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000150:complications* / Q000188:drug therapy*; D003422:Critical Care / Q000379:methods*; D003428:Cross Infection / Q000209:etiology*; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D005296:Ferrous Compounds; D006397:Hematinics; C020748:ferrous sulfate