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Preoperative Anemia Lori Heller, MD Cardiac Anesthesiologist Medical Director, Blood Management Program Swedish Medical Center Seattle, WA.

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Presentation on theme: "Preoperative Anemia Lori Heller, MD Cardiac Anesthesiologist Medical Director, Blood Management Program Swedish Medical Center Seattle, WA."— Presentation transcript:

1 Preoperative Anemia Lori Heller, MD Cardiac Anesthesiologist Medical Director, Blood Management Program Swedish Medical Center Seattle, WA

2 Outline Anemia/preoperative anemia – Outcomes Evaluation of Anemia Treatment –Iron –ESA – safety/efficacy

3 Swedish Medical Center Private, non-profit organization founded Hospitals 100 Primary and Specialty Care Clinics 2 Ambulatory Care Centers Level II Trauma Residency: Gen Surgery/Family Medicine/Podiatry Fellowships: MFM, Thoracic, Neuro, Robotic, Lap Active Robotic Surgery Program 11,000 employees in Greater Seattle

4 Cherry Hill Campus 385 beds FH Main Campus 613 beds Ballard Campus 163 beds

5 5 Swedish Orthopedic Institute 84 beds Issaquah Campus beds Edmonds Campus 217 beds

6 Blood Management Began 1999 as Bloodless Program Manager 1.5 FTE RN 0.7 FTE data assistant Medical Director – 20 hrs month

7 % Orthopedic Patients Transfused Ortho transfusion rate decreased 83% over 6 years.

8 % Hospitalists Patients Transfused % Patients transfused decreased from 32 to 23

9 Autologous Blood Utilization

10 Anemia – its prevalent! Estimated 3.5 million US Preoperative – 20-40% (Ortho, lung ca, colorectal, mixed) HCT < 39 – 25-30% HCT < 36 – 34% Elderly – 10-60% Hospitalized men HCT < % women HCT < 36 40% Community % Cardiac Surgery – 26%

11 Percent CV Pts Anemic Upon Admission

12 % Orthopedic Patients Anemic

13 Anemia Higher rates of hospitalization Decreased survival 5 yr survival 48 v. 67% (p<0.001) 8 year survival Kikuchi et al J Am Geriatr Soc 2001;49: Salive J Am Geriatr Soc 1992;40: The American Journal of Medicine Volume 119 Number 4 April 2006 Its bad!

14 Anemia Survival The American Journal of Medicine Volume 119 Number 4 April 2006 Not Anemic Anemic

15 Preoperative Anemia Its bad too!

16 Preoperative Anemia 227,425 pts RC 30 day outcome OR 1.42 mortality Even Mild Anemia Lancet 2011; 378: 1396–407

17 300,000 age > 65 (RC) Increased Mortality and Cardiac Events HCTS < 39 Preop Anemia Jama, June Vol 297 (22)

18 Preop Anemia Anesthesiology Issue: Volume 110(3), March 2009, pp Retrospective Review 8000 /Non cardiac Surg Prevalence 40% (HCT 36, 39) Adjusted for other RF and Elimination of transfusion or severe anemia Anemic Not Anemic OR 2.29 Independently Increased Mortality

19 Anesthesiology Issue: Volume 110(3), March 2009, pp Preop Anemia

20 Preoperative Evaluation A (reformed) internists perspective: Focused on cardiac status, pulmonary reserve CBC, chemistry, PFTs, cardiac stress test Coronary artery disease – consider beta blockade, perioperative nitrates and placement of Swan Ganz catheter.

21 Confession continued… Preoperative anemia ~ 34 Check Iron studies, trial of oral iron, stool guaiac, send for colon exam May need perioperative transfusion

22 CAD BE CAREFUL!!! Preoperative Evaluation Its all relative

23 % Pts Anemic on Admission

24 Improved Preop Admission Anemia Managing preop anemia

25

26 Improved Preop Admission Anemia Managing preop anemia Showing Data Canceling cases Make it easy for surgeons

27 Preoperative Anemia Assessment days in advance Flexible – finger stick hgb when convenient Prenatal Oral Iron

28 Limited in Scope Not for full work up of anemia Detection and treatment of preoperative anemia to improve surgical outcomes Always referred back to PMD!

29 Increased Destruction Marrow Failure Decreased B12/Folate/ Chemo/Myelodysplastic Decreased B12/Folate/ Chemo/Myelodysplastic Thalassemia Decreased HEME Intrinsic RBC Sideroblastic ACD Iron Def Decreased Globin Anemia Decreased Production

30 Anemia Decreased Production Increased Destruction Extravascular Hemolysis Blood Loss HGB S, C, E G6PD Immune Hemolysis HGB S, C, E G6PD Immune Hemolysis Hypersplenism Vasculitis DIC Prosthetic Valve Vasculitis DIC Prosthetic Valve Intravascular Hemolysis

31 Anemia Blah Blah Blah Blah Decreased B12/Folate/ Myelodysplastic Decreased B12/Folate/ Myelodysplastic Thalassemia Decreased Blah Blah Blah Sidero something ACD Iron Def Decreased Blah Blah

32 Give Iron Refer to Hematologist Surgeons View

33 Preoperative Anemia – NATA British Journal of Anaesthesia 106 (1): 13–22 (2011)

34 Anemia CBC MCV/RDW CBC MCV/RDW Iron Studies IV Iron B12/Folate ESA + IV iron B12 replacement IM/PO Folate Prenatal B mcg Thyroid ?ETOH c/w ACD Or normal Retic Count Other Cell lines/abnormal cells?

35 Iron Little use for oral iron as sole replacement –Limited pt compliance –Months to improve stores –Poor absorption – H2 blockers, PPI, inflammation Chromagen Forte –Vitamin C –B12 –Folate Prenatal mcg B12 + Iron

36 IV Iron Iron Dextran – Total dose replacement mg –Risk anaphylaxis –Needs pretreatment Iron Gluconate/Sucrose –Limited by dosing –125 mg QD Ferrlicet –200 mg 2-3 x week Venofer Ferumoxytol (Feraheme) –510 mg IV push (watch anaphylaxis x 30 min) –2 doses 3-8 days apart

37 Calculating Dose mg Iron for each gm/dl hgb deficit Plus mg to replace true iron stores if –tsat < 10 OR –tsat < 20 + ferritin < 100 ng/dl Normal hgb + decreased Ferritin –[100 – ferritin] x 10 Acute blood loss – mg per cc

38 FE Deficiency V. ACD FE DeficiencyAnemia of Chronic Disease Serum FE Decreased FerritinDecreasedNml or increased TIBCNl or Increased Decreased % satDecreasedNml or decreased

39 Anemia of Chronic Disease: Role of Hepcidin Andrews J Clin Invest 2004

40 Anemia Of Chronic Disease Enteric uptake inhibited Release from Macrophages Inhibited

41 Anemia of Chronic Disease- Preoperative Treatment ESA IV iron

42 ESA Use Effective Check CMS guidelines - WA –Elective Hips and Knees HCTS < 39 –All others HCTS < 33 –Not Iron deficient Give iron with ESA Goodnough Transfusion 34:66-71, 1994 J Thorac Cardiovasc Surg 2001;122: Sowade Blood :

43 ASA Statement on Transfusion 2006 Erythropoietin should be administered when possible to reduce the need for allogeneic blood in certain selectedpatient populations (e.g., renal insufficiency, anemia of chronic disease, refusal of transfusion).

44 STS 2011 Guidelines Class IIa. It is reasonable to use preoperative erythropoietin(EPO) plus iron, given several days before cardiac operation, to increase red cell mass in patients with preoperative anemia, in candidates for operation who refuse transfusion (eg, Jehovahs Witness), or in patients who are at high risk for postoperative anemia.

45 Perioperative ESAs Approved for use for pts undergoing autologous donation: –Japan 1993 –Europe 1994 –Canada 1996 Approved for perisurgical adjuvant therapy w/o auto donation –Canada/USA 1996

46 Preoperative ESAs Canadian, (+2 US studies) – 208 orthopedic pts –300 u/kg SQ x 14 days, 9 days preoperatively –+ oral iron all groups –½ rate exposure to allogeneic blood –Both groups Hgb > 130 g/L –No adverse events in treatment groups Lancet 341: , 1993 De Andrade JR: Am J Orthop 25: , 1996 Faris: J Bone J Surg 78A:62-72, 1996

47 Canadian Orthopedic Erythropoietin Study Group – Elective Hips Lancet 341: , 1993 Group 1 placebo 14 days Group u/kg EPO 9 days preop/14 days total Group 3 placebo days and 300 u/kg EPO next 9 days

48 European Epoetin Alfa Surgery Trial Multicenter trial EPO v routine (6 countries- 700 pts) Anemic pts – hgb g/dl EPO 40u/ kg/wk x 3 + DOS + iron both groups (oral treatment/iv or oral control) Results: –higher hgb levels throughout –12% v. 46% transfusion –No effect post op recovery (time ambulation, d/c, infection rate –Time to ambulation, d/c longer in transfused v. non-transfused –SE comparable Weber, Eur J Anaesthesiol April 2005;22(4):

49 European Epoetin Alfa Surgery Trial Weber, Eur J Anaesthesiol April 2005;22(4):

50 July 30, 2008 – FDA issues Complete Response letters ordering safety labeling changes under FDAAA Cancer Patients on Chemotherapy –ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure DOSAGE AND ADMINISTRATION –Therapy should not be initiated at hemoglobin levels 10 g/dL, except where the patient is unable to tolerate this degree of anemia due to co- morbid conditions –If the hemoglobin exceeds a level needed to avoid transfusion or exceeds 12 g/dL, withhold dose until the hemoglobin approaches a level where transfusion may be required U.S. Food and Drug Administration. Accessed August 7, FDA Orders ESAs Safety Labeling Changes

51 PROCRIT® (epoetin alfa) for Injection WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE Cancer: ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course. Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

52 EPO and Thrombosis RTC 680 spine pts 600 u/kg x 4 doses Rate all DVT (doppler Day 4 + sx) –Greater (4.7 v 2.1) Rate symptomatic same Post –hoc combined PE + DVT same Spine 2009; 34:

53 EPO and Renal Disease 4 major RTC – –Targeted HCTS (hgb 13-15) –One underpowered –Higher EPO dosing (3x) –Not adequate iron replacement Drueke NEJM 2006: 355 Singh AK et al N Engl J Med 2006;355: New Engl J Med 2006;355:

54 Epo and Cancer One meta analysis 51 studies –ALL Targeted hgb > 13 –O.R. VTE 1.57 –Increased tumor progression/mortality Not indicated for patients undergoing treatment for cure Bennett CL et al, JAMA. 2008;299 (8):

55 EPO and Cancer Meta analysis 60 studies No affect mortality (OR 1.06) or disease progression (OR 1.01) + VTE (OR 1.48) Glaspy J et al British Journal of Cancer 2010;102,

56 Presurgical EPO - summary Use with caution CKD, malignancy, h/o VTE Use Lowest dose (with IV iron!) Consider Thromboprophylaxis – high risk pts

57 Informed Consent Risks of Blood Transfusion include: Increased Mortality, Hemolytic Transfusion Reactions, Postoperative Infection, Malignancy Recurrence, Immunosuppression, Viral transmission, Transfusion Related Acute Lung Injury, Circulatory Overload

58 Blood Conservation in Cardiac Patients Pre surgical (including cath lab) Intraoperative Post operative

59 Presurgical/Cath Lab Blood Conservation Baseline HCT/HGB Iron studies if HCT < 37 or MCV < 80 B12/Folate levels if MCV > 100 Radial Artery Cannulation Use of U/S or Doppler Use of groin closure device Measure hematoma size Contrast image post – diagnose retroperitoneal bleed Recycle all lost blood Spring loaded introducer Post Cath HCT

60 CV Surgery Presurgical Anemia If HCT < 37 Delay if possible Aggressive IV iron –(venofer 200 mg x 3-5 doses) EPO if HCT less than 33 –600 u / kg q week x 2-4 weeks –+ IV iron Prenatal vitamins B mcg PLAVIX/P2Y12 inhibitors – measure platelet inhibition

61 CV surgery – ESA not indicated use 182 pts RCT ESA –Placebo, 300 u/kg, 150 u/kg –5 day prior, DOS and 2 d after CABG –Trend toward increased mortality (p=0.6) –4/5 deaths thrombotic/vascular possibly drug related –2/4 > 3 months after –No deaths placebo DAmbra Ann Thor Surg 1997;64:

62 Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement 75 consecutive patients- EPO + IV iron x 5 doses 59 observational cohort Post op morbidity OR 0.13 p = In hospital mortality OR 0.16 p = 0.04 Decreased postop renal failure OR 0.23 p = 0.03 Transfusion rate 67 v 93% p=0.01 LOS (median) 10 v 15 p Adjusted for Operative Risk Score, type of intervention, time of CPB, year of surgery Cladellas M, American Journal of Cardiology (Jul 2012)

63 To Review

64 NATA Guidelines, British J Anesthaesia, 106 (1) 13-22, 2011 Anemic HGB 12/13 Check Iron Studies No Obvious Source GI W/U Deficient Not Deficient Check Renal Function B12/Folate ? Retic Count ESA Give IRON Other Cell lines/abnormal cells?

65 Review IV iron important therapy IF po – give with vitamin C Prenatal/Vit B12 Consider ESA (Procrit 600 u/kg x 4 weeks) –IV iron with ESA –Caution CKD, Cardiac Surgery –Check CMS guidelines

66 Summary Preoperative Anemia – Prevalent Associated with poorer outcome and should be evaluated and treated Iron Studies mainstay of lab testing –Others CBC, Creat, Retic count, Thyroid Use of ESA and IV iron safe and effective May require delay of elective surgery All anemic patients need referral back to PMD


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