3 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
4 FH Main CampusBallard Campus163 beds613 beds385 bedsCherry Hill Campus
5 5 Swedish Orthopedic Institute Edmonds Campus 84 beds 217 beds Issaquah Campus5
6 Blood Management Began 1999 as Bloodless Program Manager 1.5 FTE RN 0.7 FTE data assistantMedical Director – 20 hrs month
7 Ortho transfusion rate decreased 83% over 6 years. % Orthopedic Patients TransfusedOrtho transfusion rate decreased 83% over 6 years.
8 % Hospitalists Patients Transfused % Patients transfused decreased from 32 to 23
13 Anemia It’s bad! Higher rates of hospitalization Decreased survival 5 yr survival 48 v. 67% (p<0.001)8 year survivalSalive J Am Geriatr Soc 1992;40:489-96Kikuchi et al J Am Geriatr Soc 2001;49:1226-8The American Journal of Medicine Volume 119 • Number 4 • April 200613
14 Anemia Survival Not Anemic Anemic The American Journal of Medicine Volume 119 • Number 4 • April 2006
16 Preoperative Anemia 227,425 pts RC 30 day outcome OR 1.42 mortality Even Mild AnemiaMild 29-36Mod less than 29Background Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes afternon-cardiac surgery are not well established. We aimed to assess the e ect of preoperative anaemia on 30-daypostoperative morbidity and mortality in patients undergoing major non-cardiac surgery.Methods We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College ofSurgeons’ National Surgical Quality Improvement Program database (a prospective validated outcomes registry from211 hospitals worldwide in 2008). We obtained anonymised data for 30-day mortality and morbidity (cardiac,respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism outcomes), demographics, andpreoperative and perioperative risk factors. We used multivariate logistic regression to assess the adjusted andmodifi ed (nine predefi ned risk factor subgroups) e ect of anaemia, which was defi ned as mild (haematocritconcentration >29–<39% in men and >29–<36% in women) or moderate-to-severe (29% in men and women) onpostoperative outcomes.Findings We obtained data for patients, of whom (30·44%) had preoperative anaemia. After adjustment,postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia (odds ratio [OR]1·42, 95% CI 1·31–1·54); this di erence was consistent in mild anaemia (1·41, 1·30–1·53) and moderate-to-severeanaemia (1·44, 1·29–1·60). Composite postoperative morbidity at 30 days was also higher in patients with anaemiathan in those without anaemia (adjusted OR 1·35, 1·30–1·40), again consistent in patients with mild anaemia (1·31,1·26–1·36) and moderate-to-severe anaemia (1·56, 1·47–1·66). When compared with patients without anaemia or adefi ned risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality andmorbidity than did patients with either anaemia or the risk factor alone.Interpretation Preoperative anaemia, even to a mild degree, is independently associatedLancet 2011; 378: 1396–407
17 Preop Anemia 300,000 age > 65 (RC) Increased Mortality and Cardiac EventsHCTS < 39wuJama, June Vol 297 (22)
18 Preop Anemia OR 2.29 Independently Increased Mortality Retrospective Review 8000 /Non cardiac SurgPrevalence 40% (HCT 36, 39)Adjusted for other RF andElimination of transfusion or severe anemiaOR 2.29Independently Increased MortalityAnemicNot AnemicAlso associated with increased risk transfusionAfter adjustment for major confounders and elimination ofpatients who were transfused or who had severe anemia,anemia was associated with increased mortality (odds ratio,2.29)AnesthesiologyIssue: Volume 110(3), March 2009, pp
19 Issue: Volume 110(3), March 2009, pp 574-581 Preop AnemiaAnesthesiologyIssue: Volume 110(3), March 2009, pp
20 Preoperative Evaluation A (reformed) internists perspective:Focused on cardiac status, pulmonary reserveCBC, chemistry, PFT’s, cardiac stress test“Coronary artery disease – consider beta blockade, perioperative nitrates and placement of Swan Ganz catheter.”
21 Confession continued… Preoperative anemia ~ 34Check Iron studies, trial of oral iron, stool guaiac, send for colon exam“May need perioperative transfusion”
22 Preoperative Evaluation It’s all relativeCADBE CAREFUL!!!
26 Improved Preop Admission Anemia Managing preop anemiaShowing DataCanceling casesMake it easy for surgeons
27 Preoperative Anemia Assessment 28-30 days in advanceFlexible – finger stick hgb when convenientHelped mrsa testingPrenatalOral Iron
28 Limited in Scope Not for full work up of anemia Detection and treatment of preoperative anemia to improve surgical outcomesAlways referred back to PMD!
29 Increased Destruction Chemo/Myelodysplastic AnemiaDecreased ProductionIncreased DestructionMarrow FailureIntrinsic RBCDecreased B12/Folate/Chemo/MyelodysplasticDecreased HEMEDecreased GlobinMarrow failure – Renal disease, endocrine red cell aplasia, tumor infiltrationNamed for the Greek words for iron and germ, sideroblastic anemia is one of the principal types of iron-utilization anemia. Abnormal, iron-saturated red cells are present in the blood of people who have this disease. Although the iron circulates normally from the plasma to the bone marrow, where new red blood cells are created, it is not properly incorporated into new red blood cells.Sideroblastic anemia can be inherited, but the disease is usually acquired as a result of illness or exposure to toxic substances.Sideroblastic anemia is a disease of adults.Iron DefACDSideroblasticThalassemia
33 Preoperative Anemia – NATA A multidisciplinary panel of physicians was convened by the Network forAdvancement of Transfusion Alternatives (NATA) with the aim of developing practiceguidelines for the detection, evaluation, and management of preoperative anaemia inelective orthopaedic surgery.British Journal of Anaesthesia 106 (1): 13–22 (2011)
34 Other Cell lines/abnormal cells? AnemiaOther Cell lines/abnormal cells?CBCMCV/RDWRetic CountOr normalIron StudiesB12/Folatec/w ACDB12 replacement IM/POFolateIV IronESA + IV ironMarrow failure – Renal disease, endocrine red cell aplasia, tumor infiltrationRetic count helpful if low (less than 0.3) or high (more than 3)Thyroid?ETOHPrenatalB mcg
35 Iron Little use for oral iron as sole replacement Chromagen Forte Limited pt complianceMonths to improve storesPoor absorption – H2 blockers, PPI, inflammationChromagen ForteVitamin CB12FolatePrenatal mcg B12 + IronIf time, ok absorption
36 IV Iron Iron Dextran – “Total dose” replacement - 1500 mg Risk anaphylaxisNeeds pretreatmentIron Gluconate/SucroseLimited by dosing125 mg QD Ferrlicet200 mg 2-3 x week VenoferFerumoxytol (Feraheme)510 mg IV push (watch anaphylaxis x 30 min)2 doses 3-8 days apart
37 Calculating Dose Normal hgb + decreased Ferritin mg Iron for each gm/dl hgb deficitPlus mg to replace true iron stores iftsat < 10ORtsat < 20 + ferritin < 100 ng/dlNormal hgb + decreased Ferritin[100 – ferritin] x 10Acute blood loss – mg per cc
38 Anemia of Chronic Disease FE Deficiency V. ACDFE DeficiencyAnemia of Chronic DiseaseSerum FEDecreasedFerritinNml or increasedTIBCNl or Increased% satNml or decreased
39 Anemia of Chronic Disease: Role of Hepcidin Why is this? There are many reasons for anemia, and I'm going to touch on them, but one very important aspect, particularly for primary care doctors, is this inflammatory process. In terms of the anemia of chronic disease that we've come to know, we're just starting to get some better idea of why this is the case. This inflammatory process of CKD is more likely than not also responsible for many of the other comorbidities we see, particularly as they pertain to CVD and peripheral vascular disease.The macrophages, when stimulated, will produce interleukin-6, which causes the hepatocytes to produce hepcidin, which blocks macrophage iron release and intestinal iron absorption. That effectively creates a situation in which iron utilization is impaired and can contribute to the anemia that we see.Iron regulatory hormone that causes sequestration of iron in macrophagesAndrews J Clin Invest 2004
40 Anemia Of Chronic Disease Enteric uptake inhibitedRelease from Macrophages Inhibited
41 Anemia of Chronic Disease- Preoperative Treatment ESAIV iron
42 ESA Use Effective Check CMS guidelines - WA Give iron with ESA Elective Hips and Knees HCTS < 39All others HCTS < 33Not Iron deficientGive iron with ESAGoodnough Transfusion 34:66-71, 1994J 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 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.”However, chronic use of EPO is associatedwith thrombotic cardiovascular events in renal failurepatients suggesting caution for this therapy inpersons at risk for such events (eg, coronary revascularizationpatients with unstable symptoms).(Level of evidence B)
45 Perioperative ESA’sApproved for use for pts undergoing autologous donation:Japan 1993Europe 1994Canada 1996Approved for perisurgical adjuvant therapy w/o auto donationCanada/USA 1996
46 Preoperative ESA’s Canadian, (+2 US studies) – 208 orthopedic pts 300 u/kg SQ x 14 days, 9 days preoperatively+ oral iron all groups½ rate exposure to allogeneic bloodBoth groups Hgb > 130 g/LNo adverse events in treatment groupsBAbstract: Concern about the risk of transmission of viral infection has led to attempts to reduce transfusion requirements in patients undergoing surgery. To determine whether recombinant human erythropoietin decreases blood transfusion requirements in patients undergoing elective hip arthroplasty, a multicentre double-blind, randomised, placebo-controlled trial was conducted. 208 patients undergoing elective primary or revision hip arthroplasty were randomised to 3 groups. All received daily subcutaneous injections of either erythropoietin or placebo starting 10 days before surgery. Group 1 (78 patients) received 14 days of placebo, group 2 (77 patients) received 14 days of erythropoietin (300 units/kg to a maximum of 30,000 units), and group 3 (53 patients) received placebo for days 10 to 6 before surgery and erythropoietin for the next 9 days. A primary outcome event (any transfusion or a haemoglobin concentration < 80 g/L) occurred in 46% of patients in group 1, 23% in group 2, and 32% in group 3 (p = 0.003). The mean number of transfusions was 1.14 in group 1, 0.52 in group 2, 0.70 in group 3. The mean reticulocyte count the day before surgery was 72 x 10(9)/L in group 1, 327 in group 2, and 170 in group 3. Deep venous thrombi were detected in 5 patients in group 1, 8 patients in group 2, and 8 patients in group 3. Patients who had a haemoglobin concentration before randomisation of < 135 g/L benefited most from erythropoietin. Thus erythropoietin given for 14 days perioperatively decreases the need for transfusion in patients undergoing elective hip arthroplasty.asis of these studies approved for perisurgical use in canda and USLancet 341: , 1993De Andrade JR: Am J Orthop 25: , 1996Faris: J Bone J Surg 78A:62-72, 1996
47 Canadian Orthopedic Erythropoietin Study Group – Elective Hips Group 1 placebo 14 daysGroup u/kg EPO 9 days preop/14 days totalGroup 3 placebo days and 300 u/kg EPO next 9 daysLancet 341: , 1993
48 European Epoetin Alfa Surgery Trial Multicenter trial EPO v routine (6 countries- 700 pts)Anemic pts – hgb g/dlEPO 40u/ kg/wk x 3 + DOS + iron both groups (oral treatment/iv or oral control)Results:higher hgb levels throughout12% v. 46% transfusionNo effect post op recovery (time ambulation, d/c, infection rateTime to ambulation, d/c longer in transfused v. non-transfusedSE comparableEffects of epoetin alfa on blood transfusions and postoperative recovery in orthopaedic surgery: the European Epoetin Alfa Surgery Trial (EEST). - Weber EW - Eur J Anaesthesiol - 01-APR-2005; 22(4): (MEDLINE is the source for the citation and abstract of this record )Abstract: BACKGROUND AND OBJECTIVE: Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications, such as postoperative infection due to immune suppression and thus hospitalization time. This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate. METHODS: In an open randomized controlled multicentre trial in patients undergoing orthopaedic surgery, the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries. Haemoglobin (Hb) values, transfusions, time to ambulation, time to discharge, infections and safety were evaluated in patients with preoperative Hb concentrations 10-13g dL(-1) (on-treatment population: epoetin n = 460; control n = 235), from study entry until 4-6 weeks after surgery. Outcome was also compared in patients with and without transfusion. RESULTS: Epoetin-treated patients had higher Hb values from the day of surgery until discharge (P < 0.001) and lower transfusion rates (12% vs. 46%; P < 0.001). Epoetin treatment delivered no significant effect on postoperative recovery (time to ambulation, time to discharge and infection rate). However, the time to ambulation (3.8+/-4.0 vs. 3.1+/-2.2days; P < 0.001)and the time to discharge (12.9+/-6.4 vs /-5.0 days; P < 0.001) was longer in the transfused than in the non-transfused patients. Side-effects in both groups were comparable. CONCLUSIONS: Epoetin alfa increases perioperative Hb concentration in mild-to-moderately anaemic patients and thus reduces transfusion requirements. Patients receiving blood transfusions require a longer hospitalization than non-transfused patients.Weber, Eur J Anaesthesiol April 2005;22(4):
49 European Epoetin Alfa Surgery Trial Weber, Eur J Anaesthesiol April 2005;22(4):
50 FDA Orders ESAs Safety Labeling Changes - 2008 July 30, 2008 – FDA issues Complete Response letters ordering safety labeling changes under FDAAACancer Patients on ChemotherapyESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cureDOSAGE AND ADMINISTRATIONTherapy 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 conditionsIf 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 requiredU.S. Food and Drug Administration. Accessed August 7, 2008.
51 PROCRIT® (epoetin alfa) for Injection WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCECancer: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 cancersESAs 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 samePost –hoc combined PE + DVT sameRCT involving 680 patients randomized to 600 U/kg epoetinalfa weekly x 4 dose (days ‐21, ‐14, ‐7, and 0) vs. standardcare– No baseline ultrasound scanning to exclude DVT– Only mechanical thromboprophylaxis allowed post‐op– Doppler screening for DVT on day 4 or if symptomatic• Rate of all DVT (doppler plus symptomatic) was greater in thetreatment group (4.7% vs. 2.1%)• Rate of symptomatic acute DVT was the same– Post‐hoc analysis of combined PE and acute DVT identical in thetwo groups– Basis of recommendation for thromboprophylaxisSpine 2009; 34: 2479‐85Spine 2009; 34: 2479‐85
53 EPO and Renal Disease 4 major RTC 1999-2009 New Engl J Med2006;355:New Engl J Med2006;355:EPO and Renal Disease4 major RTCTargeted HCTS (hgb 13-15)One underpoweredHigher EPO dosing (3x)Not adequate iron replacement11,000 v 5,000Some underpoweredecause of the non-protocolized nature of dialysis start, and the fact that there were no differences in rate of decline of GFR, or actual GFR at the time of dialysis, this finding should not be over-interpreted. It is possible that the physicians caring for the patients who knew their Hgb values, would decide to commence dialysis when symptoms worsened, in the absence of other explanations for the symptoms, while those in the lower Hgb group, who complained of symptoms, might have delayed dialysis because the symptoms were attributed to anaemia rather than uraemia.Drueke NEJM 2006: 355Singh AK et al N Engl J Med 2006;355:2085‐98
54 Epo and Cancer One meta analysis 51 studies ALL Targeted hgb > 13 O.R. VTE 1.57Increased tumor progression/mortalityNot indicated for patients undergoing treatment “for cure”qol also improvedBennett CL et al, JAMA. 2008;299 (8): 914‐924
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, 301‐315
56 Presurgical EPO - summary Use with caution CKD, malignancy, h/o VTEUse Lowest dose (with IV iron!)Consider Thromboprophylaxis – high risk pts
57 Risks of Blood Transfusion include: Informed ConsentRisks 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/HGBIron studies if HCT < 37 or MCV < 80B12/Folate levels if MCV > 100Radial Artery CannulationUse of U/S or DopplerUse of groin closure deviceMeasure hematoma sizeContrast image postdiagnose retroperitoneal bleedRecycle all lost bloodSpring loaded introducerPost Cath HCT
60 CV Surgery Presurgical Anemia If HCT < 37 Delay if possibleAggressive IV iron(venofer 200 mg x 3-5 doses)EPO if HCT less than 33600 u / kg q week x 2-4 weeks+ IV ironPrenatal vitaminsB mcgPLAVIX/P2Y12 inhibitors – measure platelet inhibition
61 CV surgery – ESA not indicated use 182 pts RCT ESAPlacebo, 300 u/kg, 150 u/kg5 day prior, DOS and 2 d after CABGTrend toward increased mortality (p=0.6)4/5 deaths thrombotic/vascular “possibly drug related”2/4 > 3 months afterNo deaths placeboD’Ambra Ann Thor Surg 1997;64:1886‐93
62 Cladellas M, American Journal of Cardiology (Jul 2012) Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve ReplacementCladellas M, American Journal of Cardiology (Jul 2012)75 consecutive patients- EPO + IV iron x 5 doses59 observational cohortPost op morbidity OR p = 0.008In hospital mortality OR p = 0.04Decreased postop renal failure OR p = 0.03Transfusion rate v 93% p=0.01LOS (median) v p- 0.01Adjusted for Operative Risk Score, type of intervention, time of CPB, year of surgeryPreoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI]0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.
64 Other Cell lines/abnormal cells? AnemicHGB 12/13Other Cell lines/abnormal cells?Check Iron StudiesCheck Renal FunctionB12/Folate? Retic CountDeficientNot DeficientNoObviousSourceESAGive IRONGI W/UNATA Guidelines, British J Anesthaesia, 106 (1) 13-22, 2011
65 Review IV iron important therapy IF po – give with vitamin C Prenatal/Vit B12Consider ESA (Procrit 600 u/kg x 4 weeks)IV iron with ESACaution CKD, Cardiac SurgeryCheck CMS guidelines
66 Summary Preoperative Anemia – Prevalent Associated with poorer outcome and should be evaluated and treatedIron Studies mainstay of lab testingOthers CBC, Creat, Retic count, ThyroidUse of ESA and IV iron safe and effectiveMay require delay of elective surgeryAll anemic patients need referral back to PMD