Preoperative Use of Parenteral Iron
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Transcript of 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
Muoz M. Vox Sanguinis. 2008; 94: 172183
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
Muoz M. Vox Sanguinis. 2008; 94: 172183
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.
Auerbach M. Am J Hematol. 2008; 83: 580588
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
Auerbach M. Am J Hematol. 2008; 83: 580588
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
Auerbach M. Am J Hematol. 2008; 83: 580588
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
Auerbach M. Am J Hematol. 2008; 83: 580588
Auerbach M. Am J Hematol. 2008; 83: 580588
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).