Preoperative Use of Parenteral Iron

Perioperative Management of Iron Deficiency AnemiaMoises Auron MD FAAP, FACP Hospital Medicine

Regulation of Iron Metabolism Normal body iron content ~ 3 to 4 g. - Hemoglobin ~ 2.5 g - Iron-containing proteins (eg, myoglobin, Ironcytochromes, catalase) ~ 400 mg - Transferrin-bound ~ 3 to 7 mg Transferrin- Storage iron (ferritin; hemosiderin) Storage varies according to gender - Men ~ 1 g (liver, spleen, and bone marrow). - Women depends on physiologic factors (menses, pregnancies, deliveries, lactation, and iron intake).

Regulation of Iron Metabolism

Muoz M. Vox Sanguinis. 2008; 94: 172183

Erythropoiesis in CKD

Kalantar-Zadeh K. Adv Chron Kid Dis. 2009; 16(2): 143-151.

Hemoglobin 64.4 kd tetramer 2 pairs of globin polypeptide chains - One pair alpha chains - One pair of non-alpha chains non Heme group single protoporphyrin IX bound to ferrous (Fe2+) ion linked covalently to each globin chain - If iron is oxidized [ferric state (Fe3+)] metHb Heme iron is linked covalently to histidine Oxygenation and deoxygenation Hb conformational

Diagnostic indicators of IDA Soluble transferrin receptors(sTfRs) sTfR sTfRferritin index (sTfRF) (sTfR Zinc protoporphyrin/heme ratio (ZPP/H) Reticulocyte hemoglobin content (CHr) Selective endoscopy Hepcidin

Clark SF. Curr Opin Gastroent. 2009; 25:122128.

Tests to assess Iron deficiency


Serum Transferrin Receptor (sTfR)

Skikne BS. Am J Hematol. 2008; 83:872875.

Indian J Pediatr 2010; 77 (2) : 179-183

Serum TfR/Ferritin Ratio sTfR as body Fe stores TfR/ferritin - valuable measure of the extent of Fe deficiency TfR/log ferritin - superior to the TfR/ferritin ratio, sTfR or ferritin in correctly distinguishing IDA vs. ACD vs. ACD from ACD + IDA (COMBI). sTfR had a sensitivity of 71% and specificity of 74% for correctly identifying iron-depleted marrow iron Ferritin which had a sensitivity of 25%, but specificity of 99%.Skikne BS. Am J Hematol. 2008; 83:872875. Means RT. Clin. Lab. Haem. 1999; 21:161167

Degree of Iron deficiency

Gasche C, et al. Inflamm Bowel Dis 2007;13:15451553

Mortality predictability in CKD

Kalantar-Zadeh K. Adv Chron Kid Dis. 2009; 16(2): 143-151.

Ganzonis formula Total Fe deficit (mg) = [Wt (kg) x (14 - actual Hb) x 0.24] + 500 (iron depot) - Blood volume 70 ml/kg of BW ~7% of body weight - Fe content of Hb 0.34% - Factor 0.24 = 0.0034 x 0.07 x 1000 (g to mg).

70 kg; Hb 9 g/dL ~ deficit of 1400 mg. Underestimation of iron depot in males - ~ 700-900 mg. 700Muoz M, et al. World J Gastroenterol 2009; 15(37): 4666-4674 Ganzoni AM. Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr. 1970;100: 301303.

Calculation of Iron deficit Blood volume (dL) = 65 (mL/kg) x body weight (kg) 100 (mL/dL) Hb deficit (g/dL) = 14.0 [patient Hb] Hb deficit (g) = Hb deficit (g/dL) x Blood volume (dL) Iron deficit (mg) = Hb deficit (g) x 3.3 (mg Fe/g Hb) Volume of parenteral Fe (mL) = Iron deficit (mg) C(mg/mL)

Schrier SL. Up To Date. Version 18.3

Calculation of Iron deficit Hemoglobin iron deficit (mg) = BW x (14 - Hgb) x (2.145) Volume of product required (mL) = BW x (14 - Hgb) x (2.145) C C = The concentration of elemental iron: Iron dextran: 50 mg/mL Iron sucrose: 20 mg/mL Ferric gluconate: 12.5 mg/mL

Schrier SL. Up To Date. Version 18.3

Algorithm for IV Iron replacement


What about IM iron? Painful Associated with gluteal sarcomas Permanent discoloration of the skin No evidence of superiority over IV

Auerbach M. Am J Hematol. 2008; 83: 580588

Parenteral Iron

Gasche C, et al. Inflamm Bowel Dis 2007;13:15451553

Other iron preparations Ferumoxytol (Feraheme ) - semi-synthetic carbohydrate-coated semicarbohydratesuperparamagnetic iron oxide nanoparticle - safe and effective when given as a rapid intravenous infusion of up to 510 mg (infusion rate: up to 30 mg/second) in patients with CKD and ESRD Safety concerns were hypotension and/or hypersensitivity reactions (anaphylaxis and/or anaphylactoid reactions). May transiently affect the diagnostic ability of MRI

http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022180lbl.pdf

Difficult beginnings Self limited arthralgias and myalgias ~ 50% - Only 1 in 87 patients had nonfatal anaphylaxis - Decreased with methylprednisolone (125 mg) before and after infusion (1998) - No relationship with infusion rate - Lack of efficacy of ASA and diphenhydramine Single case report in Lancet (1983) of meningismus - Patient with myalgia/arthralgia syndrome Oral iron - inexpensive and effective if tolerated - decreased interest in parenteral iron.


The evolution of iron preparations HMWD (DexFerrum) 1111-fold serious AE vs. LMWD (InFeD) - Anaphylactic reactions Non-dextran preparations Non- Ferric gluconate Patients with reactions have no tryptase 125 mg IV push over 510 min 5 - Iron sucrose 200 mg IV push or 300 mg over 2 hr LMWD, ferric gluconate, and iron sucrose: similar AEs - Estimated incidence of 500 ng/ ml. Fishbane IV Fe: - Decreased suboptimal response to EPO: 3040% to < 10% 30 - dosing and duration of EPO - Poor compliance and absorption avoid PO Fe - IV Fe 1g rapid improvement of erythropoiesis and replenishment of depleted stores. Administered over 10 doses. Serious AE ~ 0.7% ~ 0.3% - acute chest and back pain without BP, RR, HR, wheezing, stridor, or periorbital edema Self limited reactions.Auerbach M. Am J Hematol. 2008; 83: 580588

Iron and ESRD Hoen et al. - N = 998 hemodialysis patients - No association of ferritin levels or IV Fe administered with infections.

Clin Nephrol. 2002 Jun;57(6):457-61.

Iron in ESRD NKF-KDOQI - IV iron in preference to p.o. iron - Serum ferritin >100 ng/ mL - Continue Fe as long as ferritin 50% - IV iron can be administered: LMWD total infusion dose or repeated doses Ferric gluconate or iron sucrose repeated doses


IDA in non-dialysis CKD non-

MacDougall IC. Curr Med Res & Opin. 2010; 26(2):473482.

IV Iron in Non-dialysis CKD Non-

MacDougall IC. Curr Med Res & Opin. 2010; 26(2):473482.

Anemia of chronic disease Disturbed iron homeostasis - absorption and Fe recycling from RES - hypoferremia (low transferrin-bound iron) transferrin IBD - I.V. Fe route of choice Potential of worsening IBD with P.O. Fe


Anemia of cancer and chemotherapy Multiple studies of patients with different type of cancer on chemoradiation or chemotherapy on ESA - Randomized to ESA alone, p.o. vs. i.v. Iron IV iron - Increase in Hb > 2 g/dL - 45% decrease in allogenic blood transfusions - reduces ESA failure - Oncology no difference in tumor outcomes vs. ESA



Parenteral iron in surgery N = 84 patients Major elective surgery (30 colon cancer resections, 33 abdominal hysterectomies, 21 lower limb arthroplasties) IV iron mean dose 1000 mg + 440 mg Hb > 2.0 g/dl Resolved anemia in 58% of patients. No life-threatening AEs lifeMuoz M. Med Clin (Barc). 2009 Mar 7;132(8):303-6.

Iron in Orthopedic surgery Meta-analysis (N = 807) Meta IV iron significant decrease in: - transfusion rate [ RR: 0.60, 95% CI: 0.500.50-0.72, P < 0.001] - infection rate [RR: 0.45, 95% CI: 0.320.320.63, P < 0.001]Garca-Erce JA. Anemia 2009; 2: 17-27.

Iron in Gynecologic surgery N = 76 with Hb 60 yr old, vitamin B12 and folic acid should also be measured. Iron replacement per Ganzonis formula. Postoperatively 150 mg of i.v. iron per g/dl of Hb drop should be added to compensate iron loss due to perioperative bleeding.

Br J Anaesth 2008; 100: 599604

Preoperative Fe administration in non-anemic patients: non- Ferritin < 100 ng/ml - Ferritin 100300 ng ml and Tsat < 20% 100 - Surgery with EBL > 1500 ml (Hb drop ~f 35 g/dl) 3 IV Fe should be avoided in: - Ferritin > 300 ng/ml and Tsat > 50%. - Acute infection.

Br J Anaesth 2008; 100: 599604

Iron Adverse drug events FDA (2001 2003) - 30 million doses - 11 deaths - 1141 total ADEs Iron sucrose - 0.6 per million doses Ferric gluconate - 0.9 per million doses LMWD - 3.3 per million doses HMWD - 11.3 per million dosesChertow GM. Nephrol Dial Transplant. 2006;21(2):378-82.

Cost of IV Iron vs. Transfusion

Bieber EJ. OBG Management. 2010;22(2):28-38. Silverstein SB. Am J Hematol. 2004; 76:7478.

Recommended Preoperative IV Iron replacement Venofer (Iron sucrose) 200 mg (10 ml) administered over 10 minutes x 5 doses. Ferrlecit (Ferric gluconate) 125 mg iv over 1 hour x 8 doses (Inpatient).

Preoperative Use of Parenteral Iron

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