preoperative anemia lori heller, md cardiac anesthesiologist medical director, blood management...
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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