Preoperative Anemia

Lori Heller, MD

Cardiac Anesthesiologist

Medical Director, Blood Management Program

Swedish Medical Center

Seattle, WA

Outline

• Anemia/preoperative anemia – Outcomes

• Evaluation of Anemia

• Treatment– Iron – ESA – safety/efficacy

Swedish Medical Center

Private, non-profit organization founded 19106 Hospitals100 Primary and Specialty Care Clinics2 Ambulatory Care CentersLevel II TraumaResidency: Gen Surgery/Family Medicine/PodiatryFellowships: MFM, Thoracic , Neuro, Robotic, LapActive Robotic Surgery Program11,000 employees in Greater Seattle

Cherry Hill Campus

385 beds

FH Main Campus

613 beds

Ballard Campus

163 beds

5

Swedish Orthopedic Institute

84 beds

Issaquah Campus 80175 beds

Edmonds Campus

217 beds

Blood Management

• Began 1999 as Bloodless Program

• Manager• 1.5 FTE RN• 0.7 FTE data assistant• Medical Director – 20 hrs month

0

10

20

30

40

50

60

70

% Patients

Linear (% Patients)

% Orthopedic Patients Transfused

Ortho transfusion rate decreased 83% over 6

years.

% Hospitalists Patients Transfused

0

5

10

15

20

25

30

35

2008 Jan- Dec 2009 Jan- Dec 2010 Jan- Dec 2011 Jan- Dec

% Patients

% Patients transfused decreased from 32 to 23

Autologous Blood Utilization

Autologous Blood Ordered

68 74 87 91 830

1676

1369

1073

506

304

292942496476

72

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2006 2007 2008 2009 2010 2011

FIRST HILL

CHERRY HILL

BALLARD

Anemia – it’s 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 < 39 50-60% women HCT < 36 40%

Community - 5-59%

Cardiac Surgery – 26%

Percent CV Pts Anemic Upon Admission 2011-2012

% Orthopedic Patients Anemic

Anemia

• Higher rates of hospitalization

• Decreased survival • 5 yr survival 48 v. 67% (p<0.001)

• 8 year survivalKikuchi et al J Am Geriatr Soc 2001;49:1226-8

Salive J Am Geriatr Soc 1992;40:489-96

The American Journal of MedicineVolume 119 • Number 4 • April 2006

It’s bad!

Anemia Survival

The American Journal of MedicineVolume 119 • Number 4 • April 2006

Not Anemic

Anemic

Preoperative Anemia

It’s bad too!

Preoperative Anemia 227,425 pts RC 30 day outcomeOR 1.42 mortalityEven Mild Anemia

Lancet 2011; 378: 1396–407

300,000 age > 65 (RC)Increased Mortality and Cardiac EventsHCTS < 39

Preop Anemia

Jama, June 13 2007 Vol 297 (22)

Preop Anemia

AnesthesiologyIssue: Volume 110(3), March 2009, pp 574-581

Retrospective Review 8000 /Non cardiac SurgPrevalence 40% (HCT 36, 39)Adjusted for other RF and Elimination of transfusion or severe anemia

Anemic

Not Anemic

OR 2.29 Independently Increased Mortality

AnesthesiologyIssue: Volume 110(3), March 2009, pp 574-581

Preop Anemia

Preoperative Evaluation

A (reformed) internists perspective:Focused on cardiac status, pulmonary reserve

CBC, chemistry, PFT’s, cardiac stress test

“Coronary artery disease – consider beta blockade, perioperative nitrates

and placement of Swan Ganz catheter.”

Confession continued…

• Preoperative anemia ~ 34

• Check Iron studies, trial of oral iron, stool guaiac, send for colon exam

“May need perioperative transfusion”

CAD

BE CAREFUL!!!

Preoperative EvaluationIt’s all relative

% Pts Anemic on Admission

Improved Preop Admission Anemia

• Managing preop anemia

Improved Preop Admission Anemia

• Managing preop anemia

• Showing Data

• Canceling cases

• Make it easy for surgeons

Preoperative Anemia Assessment

• 28-30 days in advance

• Flexible – finger stick hgb when convenient

PrenatalOral Iron

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!

Increased Destruction

Marrow Failure

Decreased B12/Folate/Chemo/Myelodysplastic

Thalassemia

Decreased HEME

Intrinsic RBC

SideroblasticACD Iron Def

Decreased Globin

Anemia

Decreased Production

Anemia

Decreased Production

Increased Destruction

Extravascular Hemolysis

Blood Loss

HGB S, C, EG6PD

Immune Hemolysis

Hypersplenism

VasculitisDIC

Prosthetic Valve

Intravascular Hemolysis

Anemia

Blah Blah Blah Blah Blah

Blah

Blah Blah

Decreased B12/Folate/

Myelodysplastic

Thalassemia

Decreased Blah Blah

Blah Blah

Sidero somethingACD

Iron Def

Decreased Blah Blah

Give Iron

Refer to Hematologist

Surgeon’s View

Preoperative Anemia – NATA

British Journal of Anaesthesia 106 (1): 13–22 (2011)

Anemia

CBCMCV/RDW

Iron Studies

IV Iron

B12/Folate

ESA + IV iron

B12 replacement

IM/POFolate

PrenatalB12 500 mcg

Thyroid?ETOH

c/w ACD

Or normal Retic Count

Other Cell lines/abnormal

cells?

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 + 500 mcg B12 + Iron

IV Iron• Iron Dextran – “Total dose” replacement - 1500 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

Calculating Dose• 150-200 mg Iron for each gm/dl hgb deficit

• Plus 500-800 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

FE Deficiency V. ACD

FE Deficiency Anemia of Chronic Disease

Serum FE Decreased Decreased

Ferritin Decreased Nml or increased

TIBC Nl or Increased

Decreased

% sat Decreased Nml or decreased

Anemia of Chronic Disease: Role of Hepcidin

Andrews J Clin Invest 2004

Anemia Of Chronic Disease

• Enteric uptake inhibited

• Release from Macrophages Inhibited

Anemia of Chronic Disease- Preoperative Treatment

• ESA

• IV iron

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, 1994J Thorac Cardiovasc Surg 2001;122:741-745Sowade Blood 1997 89: 411-418

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).

STS 2011 GuidelinesClass 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, Jehovah’s Witness), or in patients who are at high risk for postoperative

anemia.”

Perioperative ESA’s• 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

Preoperative ESA’s

• 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 341:1227-1232, 1993De Andrade JR: Am J Orthop 25:533-5421, 1996Faris: J Bone J Surg 78A:62-72, 1996

Canadian Orthopedic Erythropoietin Study Group – Elective Hips

Lancet 341:1227-1232, 1993

Group 1 placebo 14 daysGroup 2 300 u/kg EPO 9 days preop/14 days totalGroup 3 placebo days -10-6 and 300 u/kg EPO next 9 days

European Epoetin Alfa Surgery Trial • Multicenter trial EPO v routine (6 countries- 700 pts)

• Anemic pts – hgb 10-13 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): 249-57

European Epoetin Alfa Surgery Trial

Weber, Eur J Anaesthesiol April 2005;22(4): 249-57

• 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. www.fda.gov/medwatch/safety/2008/safety0.8.htm#chronological. Accessed August 7, 2008.

FDA Orders ESAs Safety Labeling Changes - 2008

PROCRIT®(epoetin alfa) for InjectionWARNINGS: 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.

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: 2479‐85

EPO and Renal Disease• 4 major RTC

– 1999-2009 – Targeted HCTS 39-45 (hgb 13-15)– One underpowered– Higher EPO dosing (3x)– Not adequate iron replacement

Drueke NEJM 2006: 355Singh AK et al N Engl J Med 2006;355:2085‐98

 New Engl J Med2006;355:2071-2084.

New Engl J Med2006;355:2071-2084.

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): 914‐924

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, 301‐315

Presurgical EPO - summary

• Use with caution CKD, malignancy, h/o VTE

• Use Lowest dose (with IV iron!)

• Consider Thromboprophylaxis – high risk pts

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

Blood Conservation in Cardiac Patients

Pre surgical (including cath lab)

Intraoperative

Post operative

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

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• B12 500 mcg

PLAVIX/P2Y12 inhibitors – measure platelet inhibition

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

D’Ambra Ann Thor Surg 1997;64:1886‐93

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 = 0.008• 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- 0.01

• Adjusted for Operative Risk Score, type of intervention, time of CPB, year of surgery

Cladellas M, American Journal of Cardiology (Jul 2012)

To Review

NATA Guidelines, British J Anesthaesia, 106 (1) 13-22, 2011

Anemic HGB 12/13

Check Iron Studies

No Obvious Source

GI W/U

DeficientNot

Deficient

Check Renal Function

B12/Folate? Retic Count

ESA

Give IRON

Other Cell lines/abnormal

cells?

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

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