preoperative use of parenteral iron

Perioperative Management of Perioperative Management of Iron Deficiency AnemiaIron Deficiency Anemia

Perioperative Management of Perioperative Management of Iron Deficiency AnemiaIron Deficiency Anemia

Moises Auron MD FAAP, FACPMoises Auron MD FAAP, FACP

Hospital MedicineHospital Medicine

Disclosure of Financial RelationshipsDisclosure of Financial Relationships

• Dr. Auron has Dr. Auron has no relationshipsno relationships with entities with entities producing, marketing, re-selling, or producing, marketing, re-selling, or distributing health care goods or services distributing health care goods or services consumed by, or used on, patients.consumed by, or used on, patients.

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRD and ACDIron in CKD and ESRD and ACD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Regulation of Iron Regulation of Iron MetabolismMetabolism

Regulation of Iron Regulation of Iron MetabolismMetabolism

• Normal body iron content ~ 3 to 4 g. Normal body iron content ~ 3 to 4 g. - Hemoglobin Hemoglobin ~ 2.5 g~ 2.5 g- Iron-containing proteins (eg, myoglobin, Iron-containing proteins (eg, myoglobin,

cytochromes, catalase) ~ 400 mgcytochromes, catalase) ~ 400 mg- Transferrin-bound ~ 3 to 7 mgTransferrin-bound ~ 3 to 7 mg- Storage iron (ferritin; hemosiderin)Storage iron (ferritin; hemosiderin)

• Storage varies according to genderStorage varies according to gender- Men ~ 1 g (liver, spleen, and bone marrow). Men ~ 1 g (liver, spleen, and bone marrow). - Women – depends on physiologic factors Women – depends on physiologic factors

(menses, pregnancies, deliveries, lactation, and (menses, pregnancies, deliveries, lactation, and iron intake). iron intake).

Muñoz M. Vox Sanguinis. 2008; 94: 172–183

Regulation of Iron Regulation of Iron MetabolismMetabolism

Regulation of Iron Regulation of Iron MetabolismMetabolism

Erythropoiesis in CKDErythropoiesis in CKDErythropoiesis in CKDErythropoiesis in CKD

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

HemoglobinHemoglobinHemoglobinHemoglobin

• 64.4 kd tetramer – 2 pairs of globin polypeptide chains64.4 kd tetramer – 2 pairs of globin polypeptide chains

- One pair alpha chainsOne pair alpha chains

- One pair of non-alpha chainsOne pair of non-alpha chains

• Heme group – single protoporphyrin IX bound to ferrous Heme group – single protoporphyrin IX bound to ferrous (Fe2+) ion – linked covalently to each globin chain(Fe2+) ion – linked covalently to each globin chain

- If iron is oxidized [ferric state (Fe3+)] If iron is oxidized [ferric state (Fe3+)] metHb metHb

• Heme iron is linked covalently to histidine Heme iron is linked covalently to histidine

• Oxygenation and deoxygenation Oxygenation and deoxygenation Hb conformational ∆ Hb conformational ∆

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRD and ACDIron in CKD and ESRD and ACD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Diagnostic indicators of IDADiagnostic indicators of IDADiagnostic indicators of IDADiagnostic indicators of IDA

• Soluble transferrin receptors(sTfRs)Soluble transferrin receptors(sTfRs)

• sTfR–ferritin index (sTfR–F)sTfR–ferritin index (sTfR–F)

• Zinc protoporphyrin/heme ratio (ZPP/H)Zinc protoporphyrin/heme ratio (ZPP/H)

• Reticulocyte hemoglobin content (CHr)Reticulocyte hemoglobin content (CHr)

• Selective endoscopySelective endoscopy

• HepcidinHepcidin

Clark SF. Curr Opin Gastroent. 2009; 25:122–128.

Tests to assess Iron deficiencyTests to assess Iron deficiencyTests to assess Iron deficiencyTests to assess Iron deficiency

Muñoz M. Vox Sanguinis. 2008; 94: 172–183

Serum Transferrin Receptor (sTfR)Serum Transferrin Receptor (sTfR)Serum Transferrin Receptor (sTfR)Serum Transferrin Receptor (sTfR)

Skikne BS. Am J Hematol. 2008; 83:872–875.

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

Serum TfR/Ferritin Ratio Serum TfR/Ferritin Ratio Serum TfR/Ferritin Ratio Serum TfR/Ferritin Ratio

• sTfR ↑ as body Fe stores ↓ sTfR ↑ as body Fe stores ↓ • TfR/ferritin - valuable measure of the extent of Fe TfR/ferritin - valuable measure of the extent of Fe

deficiencydeficiency• TfR/log ferritin - superior to the TfR/ferritin ratio, TfR/log ferritin - superior to the TfR/ferritin ratio,

sTfR or ferritin in correctly distinguishing IDA vs. sTfR or ferritin in correctly distinguishing IDA vs. ACD vs. ACD from ACD + IDA (COMBI).ACD vs. ACD from ACD + IDA (COMBI).

• sTfR had a sensitivity of 71% and specificity of sTfR had a sensitivity of 71% and specificity of 74% for correctly identifying iron-depleted marrow 74% for correctly identifying iron-depleted marrow

• Ferritin which had a sensitivity of 25%, but Ferritin which had a sensitivity of 25%, but specificity of 99%.specificity of 99%.

Skikne BS. Am J Hematol. 2008; 83:872–875.Means RT. Clin. Lab. Haem. 1999; 21:161–167

Degree of Iron deficiencyDegree of Iron deficiencyDegree of Iron deficiencyDegree of Iron deficiency

Gasche C, et al. Inflamm Bowel Dis 2007;13:1545–1553

Mortality predictability in CKDMortality predictability in CKDMortality predictability in CKDMortality predictability in CKD

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

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRD and ACDIron in CKD and ESRD and ACD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Ganzoni’s formulaGanzoni’s formulaGanzoni’s formulaGanzoni’s formula• Total Fe deficit (mg) = [Wt (kg) x Total Fe deficit (mg) = [Wt (kg) x (14 - actual Hb) x 0.24] + (14 - actual Hb) x 0.24] +

500500 (iron depot)(iron depot)

- Blood volume 70 ml/kg of BW ~7% of body weightBlood volume 70 ml/kg of BW ~7% of body weight

- Fe content of Hb 0.34%Fe content of Hb 0.34%

- Factor 0.24 = 0.0034 x 0.07 x 1000 (g to mg).Factor 0.24 = 0.0034 x 0.07 x 1000 (g to mg).

• 70 kg; Hb 9 g/dL ~ deficit of 1400 mg. 70 kg; Hb 9 g/dL ~ deficit of 1400 mg. • Underestimation of iron depot in malesUnderestimation of iron depot in males

- ~ 700-900 mg.~ 700-900 mg.

Muñoz M, et al. World J Gastroenterol 2009; 15(37): 4666-4674Ganzoni AM. Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr. 1970;100: 301–303.

Calculation of Iron deficitCalculation of Iron deficitCalculation of Iron deficitCalculation of Iron deficit

• Blood volume (dL) Blood volume (dL) = 65 (mL/kg) x body weight (kg) ÷ 100 (mL/dL)= 65 (mL/kg) x body weight (kg) ÷ 100 (mL/dL)

• Hb deficit (g/dL)Hb deficit (g/dL) = 14.0 – [patient Hb] = 14.0 – [patient Hb]

• Hb deficit (g)Hb deficit (g) = = Hb deficit (g/dL)Hb deficit (g/dL) x x Blood volume (dL) Blood volume (dL)

• Iron deficit (mg)Iron deficit (mg) = = Hb deficit (g)Hb deficit (g) x 3.3 (mg Fe/g Hb) x 3.3 (mg Fe/g Hb)

• Volume of parenteral Fe (mL)Volume of parenteral Fe (mL) = = Iron deficit (mg)Iron deficit (mg) ÷ C(mg/mL) ÷ C(mg/mL)

Schrier SL. Up To Date. Version 18.3

• Hemoglobin iron deficit (mg) = BW x (14 - Hgb) x (2.145) Hemoglobin iron deficit (mg) = BW x (14 - Hgb) x (2.145)

• Volume of product required (mL) = BW x (14 - Hgb) x (2.145) ÷ C Volume of product required (mL) = BW x (14 - Hgb) x (2.145) ÷ C

• C = The concentration of elemental iron: C = The concentration of elemental iron:

• Iron dextran: 50 mg/mL Iron dextran: 50 mg/mL

• Iron sucrose: 20 mg/mL Iron sucrose: 20 mg/mL

• Ferric gluconate: 12.5 mg/mLFerric gluconate: 12.5 mg/mL

Calculation of Iron deficitCalculation of Iron deficitCalculation of Iron deficitCalculation of Iron deficit

Schrier SL. Up To Date. Version 18.3

Algorithm for IV Iron Algorithm for IV Iron replacementreplacement

Algorithm for IV Iron Algorithm for IV Iron replacementreplacement

Muñoz M. Vox Sanguinis. 2008; 94: 172–183

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRD and ACDIron in CKD and ESRD and ACD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

What about IM iron?What about IM iron?What about IM iron?What about IM iron?

• PainfulPainful

• Associated with gluteal sarcomas Associated with gluteal sarcomas

• Permanent discoloration of the skinPermanent discoloration of the skin

• No evidence of superiority over IVNo evidence of superiority over IV

Auerbach M. Am J Hematol. 2008; 83: 580–588

Parenteral IronParenteral IronParenteral IronParenteral Iron

Gasche C, et al. Inflamm Bowel Dis 2007;13:1545–1553.http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022180lbl.pdf

Name Molecular Anaphylaxis Test dose [Fe] Max Weight (kD) required (mg/ml) Dose

Dextran - HMW (Dexferrum®) 265 Y Y 50 1g - LMW (Infed®) 165 Y Y 50 1g

Fe gluconate (Ferrlecit®) < 50 N N 12.5 125mg

Fe sucrose (Venofer®) 30-100 N N 20 200mg

Other iron preparationsOther iron preparationsOther iron preparationsOther iron preparations• Ferumoxytol (Feraheme ®)Ferumoxytol (Feraheme ®)

- semi-synthetic carbohydrate-coated semi-synthetic carbohydrate-coated superparamagnetic iron oxide nanoparticlesuperparamagnetic iron oxide nanoparticle

- safe and effective when given as a rapid intravenous safe and effective when given as a rapid intravenous infusion of up to 510 mg (infusion rate: up to 30 infusion of up to 510 mg (infusion rate: up to 30 mg/second) in patients with CKD and ESRDmg/second) in patients with CKD and ESRD

• Safety concerns were hypotension and/or hypersensitivity Safety concerns were hypotension and/or hypersensitivity reactions (anaphylaxis and/or anaphylactoid reactions). reactions (anaphylaxis and/or anaphylactoid reactions).

• May transiently affect the diagnostic ability of MRIMay transiently affect the diagnostic ability of MRI

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

Difficult beginningsDifficult beginningsDifficult beginningsDifficult beginnings• Self limited arthralgias and myalgias ~ 50%Self limited arthralgias and myalgias ~ 50%

- Only 1 in 87 patients had nonfatal anaphylaxisOnly 1 in 87 patients had nonfatal anaphylaxis- Decreased with methylprednisolone (125 mg) Decreased with methylprednisolone (125 mg)

before and after infusion (1998)before and after infusion (1998)- No relationship with infusion rateNo relationship with infusion rate- Lack of efficacy of ASA and diphenhydramineLack of efficacy of ASA and diphenhydramine

• Single case report in Lancet (1983) of meningismusSingle case report in Lancet (1983) of meningismus- Patient with myalgia/arthralgia syndromePatient with myalgia/arthralgia syndrome

• Oral iron - inexpensive and effective if toleratedOral iron - inexpensive and effective if tolerated- decreased interest in parenteral iron. decreased interest in parenteral iron.

Auerbach M. Am J Hematol. 2008; 83: 580–588

The evolution of iron preparationsThe evolution of iron preparationsThe evolution of iron preparationsThe evolution of iron preparations

• HMWD (DexFerrum)HMWD (DexFerrum) ↑ 11-fold serious AE vs. LMWD (InFeD) ↑ 11-fold serious AE vs. LMWD (InFeD)

- Anaphylactic reactionsAnaphylactic reactions• Non-dextran preparationsNon-dextran preparations

- Ferric gluconateFerric gluconate• Patients with reactions – have no ↑ tryptase Patients with reactions – have no ↑ tryptase • 125 mg IV push over 5–10 min125 mg IV push over 5–10 min

- Iron sucroseIron sucrose• 200 mg IV push or 300 mg over 2 hr200 mg IV push or 300 mg over 2 hr

• LMWD, ferric gluconate, and iron sucrose: LMWD, ferric gluconate, and iron sucrose: similar AE’ssimilar AE’s

- Estimated incidence of <1:200,000.Estimated incidence of <1:200,000.

Auerbach M. Am J Hematol. 2008; 83: 580–588

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRD and ACDIron in CKD and ESRD and ACD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Iron in ESRDIron in ESRDIron in ESRDIron in ESRD• Eschbach (1987) Eschbach (1987) 1g IV Fe dextran in dialysis patients failing to 1g IV Fe dextran in dialysis patients failing to

respond to EPO (standard dose of 50 U/kg 3 x wk) despite Ferritin > 500 respond to EPO (standard dose of 50 U/kg 3 x wk) despite Ferritin > 500 ng/ ml.ng/ ml.

• Fishbane Fishbane IV Fe: IV Fe:- Decreased suboptimal response to EPO: 30–40% to < 10% Decreased suboptimal response to EPO: 30–40% to < 10% - ↓ ↓ dosing and duration of EPOdosing and duration of EPO- Poor compliance and ↓absorption Poor compliance and ↓absorption avoid PO Fe avoid PO Fe- IV Fe 1g IV Fe 1g rapid improvement of erythropoiesis and replenishment rapid improvement of erythropoiesis and replenishment

of depleted stores. of depleted stores. • Administered over 10 doses.Administered over 10 doses.• Serious AE ~ 0.7%Serious AE ~ 0.7%• ~ 0.3% - acute chest and back pain without ↓BP, ↑RR, ↑HR, ~ 0.3% - acute chest and back pain without ↓BP, ↑RR, ↑HR,

wheezing, stridor, or periorbital edemawheezing, stridor, or periorbital edema• Self limited reactions.Self limited reactions.

Auerbach M. Am J Hematol. 2008; 83: 580–588

Iron and ESRDIron and ESRDIron and ESRDIron and ESRD

• Hoen et al. Hoen et al.

- N = 998 hemodialysis patientsN = 998 hemodialysis patients

- No association of ferritin levels or IV Fe No association of ferritin levels or IV Fe administered with infections.administered with infections.

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

IDA in UremiaIDA in UremiaIDA in UremiaIDA in Uremia

• Bacterial overgrowthBacterial overgrowth

• GI bleedingGI bleeding

- Platelet dysfunctionPlatelet dysfunction

- Anti-plateletsAnti-platelets

• Frequent phlebotomyFrequent phlebotomy

• ProteinuriaProteinuria

• ↑ ↑ Fe utilization (ESA)Fe utilization (ESA)

MacDougall IC. Curr Med Res & Opin. 2010; 26(2):473–482.

• ↓ ↓ Dietary sourceDietary source

- AnorexiaAnorexia

- Low protein dietLow protein diet

• ↓ ↓ GI absorptionGI absorption

- HepcidinHepcidin

- PO4 binders, CaPO4 binders, Ca2+2+

- AchlorhydriaAchlorhydria

- Atrophic gastritisAtrophic gastritis

Iron in ESRDIron in ESRDIron in ESRDIron in ESRD

• NKF-KDOQI NKF-KDOQI

- IV iron in preference to p.o. ironIV iron in preference to p.o. iron

- Serum ferritin >100 ng/ mLSerum ferritin >100 ng/ mL

- Hold Fe if Hold Fe if ferritin > 800 ng/mLferritin > 800 ng/mL and and Tsat > 50%Tsat > 50%

- IV iron can be administered:IV iron can be administered:• LMWD – total infusion dose or repeated doses LMWD – total infusion dose or repeated doses • Ferric gluconate or iron sucrose – repeated dosesFerric gluconate or iron sucrose – repeated doses

Auerbach M. Am J Hematol. 2008; 83: 580–588

IV Iron in Non-dialysis CKDIV Iron in Non-dialysis CKDIV Iron in Non-dialysis CKDIV Iron in Non-dialysis CKD

MacDougall IC. Curr Med Res & Opin. 2010; 26(2):473–482.

Anemia of chronic diseaseAnemia of chronic diseaseAnemia of chronic diseaseAnemia of chronic disease

• Disturbed iron homeostasis Disturbed iron homeostasis

- ↓ ↓ absorption and ↓ Fe recycling from RESabsorption and ↓ Fe recycling from RES

- hypoferremia (low transferrin-bound iron) hypoferremia (low transferrin-bound iron)

• IBDIBD

- I.V. Fe – route of choiceI.V. Fe – route of choice

• Potential of worsening IBD with P.O. FePotential of worsening IBD with P.O. Fe

Auerbach M. Am J Hematol. 2008; 83: 580–588

Anemia of cancer and chemotherapyAnemia of cancer and chemotherapyAnemia of cancer and chemotherapyAnemia of cancer and chemotherapy

• Multiple studies of patients with different type of cancer Multiple studies of patients with different type of cancer on chemoradiation or chemotherapy on ESA on chemoradiation or chemotherapy on ESA

- Randomized to ESA alone, p.o. vs. i.v. IronRandomized to ESA alone, p.o. vs. i.v. Iron

• IV ironIV iron

- Increase in Hb > 2 g/dLIncrease in Hb > 2 g/dL

- 45% decrease in allogenic blood transfusions45% decrease in allogenic blood transfusions

- reduces ESA failurereduces ESA failure

- Oncology – no difference in tumor outcomes vs. ESAOncology – no difference in tumor outcomes vs. ESA

Auerbach M. Am J Hematol. 2008; 83: 580–588

Auerbach M. Am J Hematol. 2008; 83: 580–588

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRDIron in CKD and ESRD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Parenteral iron in surgeryParenteral iron in surgeryParenteral iron in surgeryParenteral iron in surgery• Efficacy of IV Iron Efficacy of IV Iron

- Major elective surgery (N = 84)Major elective surgery (N = 84)

• 33 CORS, 33 Gynecologic, 21 Ortho33 CORS, 33 Gynecologic, 21 Ortho

- IV iron mean dose 1000 mg IV iron mean dose 1000 mg ++ 440 mg 440 mg

• Hb > 2.0 g/dlHb > 2.0 g/dl

• Resolved anemia ~ 58% of casesResolved anemia ~ 58% of cases

• No life-threatening AE’sNo life-threatening AE’s

• Oral vs. IV Iron Oral vs. IV Iron

- Gynecologic surgery (N = 76; Hb <9.0 g/dl)Gynecologic surgery (N = 76; Hb <9.0 g/dl)

- IV Fe sucrose 3/wk vs. daily PO Fe succinylateIV Fe sucrose 3/wk vs. daily PO Fe succinylate

• Hb (3.0 vs. 0.8 g/dl; Hb (3.0 vs. 0.8 g/dl; p < 0.0001p < 0.0001) )

• Ferritin levels (170.1 vs. 4.1 microg/l; Ferritin levels (170.1 vs. 4.1 microg/l; P<0.0001P<0.0001) )

• Target Hb (76.7% vs. 11.5%; Target Hb (76.7% vs. 11.5%; p < 0.0001p < 0.0001).).

Muñoz M. Med Clin (Barc). 2009 Mar 7;132(8):303-6. García-Erce JA. Anemia 2009; 2: 17-27.Kim YH. Acta Haematol. 2009;121(1):37-41.

IV IronIV IronIV IronIV Iron• Orthopedic surgeryOrthopedic surgery

- Meta-analysis (N = 807)Meta-analysis (N = 807)

- transfusion rate [transfusion rate [RR: 0.60RR: 0.60, 95% CI: 0.50-0.72, P < 0.001] , 95% CI: 0.50-0.72, P < 0.001]

- infection rate [infection rate [RR: 0.45RR: 0.45, 95% CI: 0.32-0.63, P < 0.001], 95% CI: 0.32-0.63, P < 0.001]

• Colorectal surgeryColorectal surgery

- 43 colorectal cancer patient43 colorectal cancer patient

• Transfusion index 4.0 vs. 1.3 unit/patientTransfusion index 4.0 vs. 1.3 unit/patient

• IV antibiotics (33% vs. 9%)IV antibiotics (33% vs. 9%)

García-Erce JA. Anemia 2009; 2: 17-27.Kim YH. Acta Haematol. 2009;121(1):37-41.Muñoz M. Semin Hematol. 2006; 43:S36-8

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRDIron in CKD and ESRD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

Potential negative effects of Potential negative effects of intravenous ironintravenous iron

Potential negative effects of Potential negative effects of intravenous ironintravenous iron

• Pro-oxidant Pro-oxidant - might increase oxidative stress, - might increase oxidative stress, infections, mortality, tumor growth. infections, mortality, tumor growth. - p.o. Iron - worsening IBD (Fenton reaction)p.o. Iron - worsening IBD (Fenton reaction)

• Non-ESRD patients – nephrotoxicity?Non-ESRD patients – nephrotoxicity?- Transient increase in induced proteinuria and Transient increase in induced proteinuria and

albuminuria with iron sucrose. albuminuria with iron sucrose. - Ferric gluconate showed significant increases in Ferric gluconate showed significant increases in

lipid peroxidation. lipid peroxidation.

Auerbach M. Am J Hematol. 2008; 83: 580–588

Iron and infectious diseasesIron and infectious diseasesIron and infectious diseasesIron and infectious diseases

Weinberg ED. Emerg Infect Dis 1999;5:346—52.

Body iron and diseaseBody iron and diseaseBody iron and diseaseBody iron and disease

Weinberg ED. Emerg Infect Dis 1999;5:346—52.

Iron Adverse drug eventsIron Adverse drug eventsIron Adverse drug eventsIron Adverse drug events

• FDA (2001 – 2003)FDA (2001 – 2003)

- 30 million doses30 million doses

- 11 deaths 11 deaths

- 1141 total ADEs 1141 total ADEs

• Iron sucrose - 0.6 per million doses Iron sucrose - 0.6 per million doses

• Ferric gluconate - 0.9 per million doses Ferric gluconate - 0.9 per million doses

• LMWD - 3.3 per million doses LMWD - 3.3 per million doses

• HMWD - 11.3 per million dosesHMWD - 11.3 per million doses

Chertow GM. Nephrol Dial Transplant. 2006;21(2):378-82.

OutlineOutlineOutlineOutline

• Iron metabolismIron metabolism• Diagnosis of IDADiagnosis of IDA• Calculation of Iron deficitCalculation of Iron deficit• Iron preparationsIron preparations• Iron in CKD and ESRDIron in CKD and ESRD• Iron in SurgeryIron in Surgery• Adverse effects of parenteral ironAdverse effects of parenteral iron• CCF Preoperative Iron replacement algorithmCCF Preoperative Iron replacement algorithm

• NATA (Network for Advancement of Transfusion Alternatives)NATA (Network for Advancement of Transfusion Alternatives)

- 2 RCT2 RCT

- 6 Observational studies6 Observational studies

• Preoperative Fe therapy Preoperative Fe therapy ↓ 2/3 ↓ 2/3 Blood TransfusionBlood Transfusion

• IV Iron: IV Iron: Ferritin < 100, Tsat < 20%, EBL > 1500 mlFerritin < 100, Tsat < 20%, EBL > 1500 ml

• Avoid IV Iron if Ferritin > 300 ng/ml and Tsat > 50%.Avoid IV Iron if Ferritin > 300 ng/ml and Tsat > 50%.

- Acute infection.Acute infection.

• Quality of Evidence is weakQuality of Evidence is weak

• Recommend large RCTRecommend large RCT

Br J Anaesth 2008; 100: 599–604.

Cost of IV Iron vs. TransfusionCost of IV Iron vs. TransfusionCost of IV Iron vs. TransfusionCost of IV Iron vs. Transfusion

Bieber EJ. OBG Management. 2010;22(2):28-38.Silverstein SB. Am J Hematol. 2004; 76:74–78.Shander A. Transfusion. 2010:50:753-65

• Iron dextran ~ $377 per gramIron dextran ~ $377 per gram

• Iron gluconate ~ $688 per gramIron gluconate ~ $688 per gram

• Iron sucrose ~ $688 per gramIron sucrose ~ $688 per gram

• Hemoglobin ~ $761 +/- 294 per unit (~250 Hemoglobin ~ $761 +/- 294 per unit (~250 mg) x 4 = mg) x 4 = $ 3044 per gram$ 3044 per gram

Recommended Preoperative IV Recommended Preoperative IV Iron replacementIron replacement

Recommended Preoperative IV Recommended Preoperative IV Iron replacementIron replacement

• Venofer (Iron sucrose) 200 mg (10 ml) Venofer (Iron sucrose) 200 mg (10 ml) administered over 10 minutes x 5 administered over 10 minutes x 5 doses.doses.

• Ferrlecit (Ferric gluconate) 125 mg iv Ferrlecit (Ferric gluconate) 125 mg iv over 1 hour x 8 doses (Inpatient). over 1 hour x 8 doses (Inpatient).