Presentation on theme: "Comprehensive Patient Blood Management"— Presentation transcript:
1 Comprehensive Patient Blood Management Avoiding Allogeneic Transfusion: A Case Study in Patient Blood ManagementIrwin Gross, M.D.May, 2012
2 Disclosures Irwin Gross, MD Medical Advisory Board, Strategic Healthcare Group
3 Learning Objectives Name the three pillars of patient blood management Name three adverse outcomes associated with transfusionList four tools that can be used in patient blood management to limit the risk of transfusionDescribe the role of parenteral iron in treating anemiaName two types of perioperative autologous blood collectionList two relative contraindications to cell salvage
5 5-75% incidence in patients presenting for elective surgery Anemia independently associated with increased:morbidityhospital length of staylikelihood of transfusionmortalitySpahn DR. Anesthesiology 2010; 113(2) 1-14Beattie WS, et al Anesthesiology 2009; 110(3)Dunne JR, et al J Surg Res 2002; 102:Shander A. Am J Med 2004; 116(7A) 58S-69S5-75% incidence in patients presenting for elective surgeryShander 2004AnemiaBleeding associated with increasedMorbidityICU and hospital length of stayMortalityElective surgery ~0.1%Subgroups:Vascular 5–8%Up to 20% with severe bleedingMajor organ damage 30–40%CausesOn average 75 – 90% local surgical interruption or vessel interruption10–25% acquired or congenital coagulopathyShander A. Surgery 2007Proceduralbood loss & bleedingRBC transfusion independently associated in a dose-dependent relationship with increased:MorbidityICU and hospital length ofstayMortalityBeattie WA, et al Anesthesiology 2009Murphy GJ, et al Circulation 2007Salim A, et al J Am Coll Surg 2008Bernard AC, et al J Am Coll Surg 2008BleedingTransfusionHearnshaw SA, et al Aliment Pharmacol Ther 2010Blair SD, et al Br J Surg 1986
6 Impact of Transfusion on Patient Outcomes Author (year)PopulationnImpact of Blood TransfusionKoch et al (2005)Cardiac surgery11,963- Higher postop mortality rate- Higher postop morbidity rate (RF, prolonged ventilatory support, serious infection, cardiac complications, & neurologic events)Murphy et al (2007)8,598- Higher mortality rate- More ischemic complications- More infectious complicationsSurgenor et al (2009)3,254- Decreased survival after cardiac surgeryPedersen et al (2009)Total hip replacement4,508- More pneumoniaNikolsky et al (2009)PCI after MI2,060- Higher 30-day and 1-year mortality ratevan Straten et al (2010)10,435- Worse early survivalD’Ayala et al (2010)Lower extremity amputation300- More postop adverse events- Longer ICU/hospital stayO’Keeffe et al (2010)Lower extremity revascularization8,799- More pulmonary complicationsVeenith et al (2010)Elderly undergoing cardiac surgery874In multiple studies, transfusion is associated with an increase in mortality, and increase in length of stay, and increase in infections, and an increase in ischemic complications. Some data suggest a decrease in survival in oncologic patients who are transfused when matched to similar patients without transfusion
7 Physiologic Impact of Red Cell Transfusion Author (year)PopulationnBlood Transfused↑Hb↑DO2↑VO2↓LactateBabineau et al (1992)Postoperative31328 ± 9 mLYesNoSilverman et al (1992)Septic shock 21–88 yrs212 unitsMarik et al (1993)Septic adults233 unitsLorente et al (1993)16?Gramm et al (1996)Septic shock 46 ± 3 yrs19Casutt et al (1999)Postoperative 32–81 yrs67368 ± 10 mLFernandes et al (2001)Septic shock 18–80 yrs101 unitsWalsh et al (2004)Euvolemic anemic critically ill patients22Suttner et al (2004)Volume-res mechanically ventilated patients511 or 2 units vs. 100% FiO2Mazza et al (2005)SIRS/Sepsis291–3 unitsWhile transfusion increases the delivery of oxygen, most studies fail to show and increase in oxygen utilization or an improvement in tissue ischemia as characterized by a decrease in lactate
8 What are “Transfusion Alternatives”? Optimize hemodynamics and oxygenationPhysiologic tolerance of anemiaUse of erythropoietic stimulating agentsUse of intravenous ironMinimizing blood lossManage coagulopathyAnti-fibrinolyticsPerioperative cell collection and reinfusion
9 Our PatientA 68 year old retired immunology professor requires revision of a prior right hip arthroplasty due to aseptic loosening with severe instability and functional limitationPast medical history is significant for rheumatoid arthritis and Type 1 vWDPatient underwent a recent hemicolectomy for T1N0M0 (Stage 1) colon cancer at another hospital without a blood management program
10 Our Patient The patient is referred to an orthopedic surgeon A total hip arthroplasty is plannedThe patient, having read the article summarized on the next slide, requests that transfusion of allogeneic blood be avoided unless surgical bleeding is life threatening
11 Influence of Transfusion on Colorectal Cancer Recurrence Cochrane meta-analysis involving 12,127 patientsEvaluated role of transfusion in colorectal cancer recurrenceOverall OR for recurrence was 1.41 (95% CI ) in transfused patientsAmato, A, et al. Cochrane Database System Rev 2006;(1): CD005033
12 Reasons to Avoid Transfusion Transfusion is associated with:Increased perioperative infectionsIncreased length of stayIncreased short term mortalityTransfusion reactions, some life threateningIncreased incidence of cancer recurrence and decreased disease-free and long term survival
13 Pre-operative Screening for Anemia The patient should be screened for anemia -he is undergoing surgery with significant blood lossCBCIf CBC shows anemia (< 13 g/dL) then additional lab tests requiredIron, iron binding capacity, ferritin, Vitamin B12, creatinine, reticulocyte countFolate if MCV > 100 flA preoperative hemoglobin less than 13 g/dl is used as a threshold for further evaluation of anemia regardless of gender. While women tend to have lower hgb levels than men, they are also at higher risk for transfusion regardless of hgb level due to lower blood volume and smaller body mass. Starting Hgb level < 13 g/dl is associated with an increase in mortality in the perisurgical population
14 SchedulingThe ideal window to evaluate a patient for pre-operative anemia is days before surgeryMedicare will not pay for lab studies > 30 daysIf commercial insurance or known history of anemia or co-morbidity associated with anemia, screen sooner (more time to treat anemia is better)Treatment of chronic anemia with iron, EPO or both requires (at least) 3-4 weeksThe clinical condition may require the case to be scheduled sooner (unstable cardiac disease; cancer diagnosis)
15 SchedulingIf procedure is truly elective, and anemia cannot be managed in the available time, surgery should be deferredOccasional patients will need referral to specialist: hematologist, gastroenterologist, etc.
16 Our PatientSurgery is scheduled to take place in 24 days. Lab results are as follows:Iron: ug/dL (28-170)Total iron binding: ug/dL ( )% Saturation: % (15-45)Ferritin ng/mL (45-500)Hemoglobin g/dL (14-17)Reticulocyte count Th/uL (22-98)Ferritin may be elevated in patients with iron deficiency due to inflammation; ferritin is an acute phase reactant.
17 Our Patient Diagnoses Recommended Rx Iron deficiency anemia (blood loss from recent chronic lower GI blood loss and colon surgery treated with enteral iron sulfate)Enteric iron is ineffective when there is inflammation, e.g. rheumatoid arthritisAnemia of Inflammation (functional iron deficiency – patient has rheumatoid arthritis)Recommended RxIntravenous ironConsider erythropoietinOral iron is poorly tolerated with a 30-40% non-compliance rate.
18 Anemia Management: Intravenous Iron / EPO “Standard” regimen for perioperative anemia; hemoglobin between g/dL; non-vascular, non-cardiac surgery40,000 units of erythropoietin on days 21, 14, and 7 pre-op, and on day of surgeryPatient must have transferrin saturation > 20% and ferritin > 100 ng/ml to be reimbursed by Medicare200 mg I.V. iron sucrose with each EPO dose1 mg folate, p.o., daily500 mg Vitamin C, twice dailySince the use of an ESA can result in functional iron deficiency, I recommend that IV iron be co-adminstered to a patient receiving ESA treatment unless there is iron oevrload or a history of hemochromatosis.
19 Should We Use EPO and Iron or Iron Alone? Reasons to use EPO:Patient has only 24 days till surgery with Hgb of 10.1 g/dlEPO improves rate of response to ironRheumatoid arthritis may result in decreased endogenous EPO productionReasons not to use EPOIncreased VTE riskSome data suggests shortened survival and time to recurrence in some malignancies with EPOBut, transfusion is associated with shortened survival and time to recurrence in malignancy and increased perisurgical mortalityJAMA. 2008;299 (8):Anesthesiology Mar; 1 10(3):547-81
20 Our PatientAfter discussion of the risks and benefits of EPO (informed consent), the patient consents to the use of EPOOrders are written for three doses of EPO between now and surgery, by subcutaneous injection (600 units/kg)A fourth dose of EPO will be given on post-op day one if hemoglobin is less than 8.0 g/dLGoal: lowest dose to avoid transfusion
21 Iron AdministrationIntravenous iron should always be given during a course of treatment with EPO unless iron saturation is > 35% or ferritin > 1,000 ng/mlThree “classes” of IV iron available in U.S.Minimal cross reactivity re: reactionsIron sucrose and iron gluconateFerumoxytol (paramagnetic nanoparticle)Iron dextransFewer ADE’s with low molecular weight iron dextran than high molecular weight iron dextran)David H et al Oncologist 12: , 2007J Am Soc Nephrol 18: , 2007
22 Iron Sucrose vs. Iron Dextran vs. Ferumoxytol Most appropriate for serial encounters or total dose of 300 mg or lessComes in 100 mg vialsMaximum dose we use is 300 mg in 100 ml saline over 60 minutesLowest rate of serious adverse drug reactionsCharacteristics and use of iron gluconate are similar
23 Iron Sucrose vs. Iron Dextran vs. Ferumoxytol Low molecular weight iron dextranBest option for total dose iron replacement (TDI)Use when single encounter and iron required exceeds mgRequires administration of test doseRemaining dose given over 1 – 2.5 hours, up to 1,500 mgLow incidence of A.D.E.’s (3.3 / million doses)I recommend against high molecular weight iron dextranLow molecular weight iron dextran is the least expensive way to administer total dose iron replacement but with a somewhat higher adverse drug reaction rate.
24 Iron Sucrose vs. Iron Dextran vs. Ferumoxytol Can administer 510 mg of iron in 17 seconds (30 mg/sec)No test dose requiredLeast experience, but seems to have a good safety profileHigher drug cost than other options
25 What about Enteric Iron? Hepcidin, Inflammation and Iron Metabolism30-40% with significant GI side effectsJ Am Soc Nephrol18: , 2007
26 Contraindications to Iron Theoretical concern in infection / sepsis – some bacteria use iron as a growth factorBut remember, transfused blood provides iron in the form of hemeImmunomodulation increases risk of infection
27 S. aureus and Iron-regulated Surface Determinant (IsdB) . Host Specificity of Staphylococcus aureus. S. aureus uses the iron-regulated surface determinant (Isd) group of proteins to acquire iron from hemoglobin. It secretes a hemolytic toxin that releases hemoglobin from red cells. The released hemoglobin then binds to the staphylococcal receptor, iron surface determinant B (IsdB) on the bacterial cell surface. Heme is extracted from hemoglobin and is transported across the cell wall and cytoplasmic membrane by other Isd proteins. After its release from heme, iron becomes available as a nutrient within the bacterial cell. The increased affinity of the S. aureus IsdB for human hemoglobin (Panel A) versus mouse hemoglobin (Panel B) accounts for the enhanced availability of iron and, in part, for the host specificity of S. aureus.Lowy FD. N Engl J Med 2011;364:
29 Our PatientWith each EPO dose, we decide to give our patient 200 mg of I.V. iron sucrose (600 mg total)Additional iron will be given post-op based on post-op hemoglobinApproximately 500 mg iron required to replace depleted storesNeed additional 150 mg for each g/dL decrease in hemoglobin below 13 g/dL
30 Our PatientOn the day of admission, our patient has a hemoglobin of 12.8 g/dL and an elevated reticulocyte countThe patient signs informed consent for transfusion only if needed to prevent death from severe hemorrhage
31 Intraoperative Management – Day of Surgery Acute normovolemic hemodilution (ANH)Intraoperative autologous blood collection and re-adminstration (“cell salvage”)DDAVPAnti-fibrinolytics (e.g. tranexamic acidMeticulous surgical hemostasisA multi-modal approach is most effective in reducing surgical blood loss.
32 Acute Normovolemic Hemodilution Conservation of red cell mass by decreasing hematocrit of shed bloodFresh whole blood, with intact platelets and clotting factors, available at end of case for transfusionStudies show reduced blood loss in joint arthroplasty, spine surgery, cardiac, hepatic resection, major colon operations, and radical cystectomyANH can contribute to a reduction in blood loss but the reduction, based on mathematical models, is relatively small when compared to some other perioperative blood management strategies
33 Acute Normovolemic Hemodilution – How Is It Done Replace volume with crystalloid or colloidWe generally use HES (tetrastarch)Usually requires 10 minutes / unitProper labelingBlood typically remains at room temperature in O.R. prior to reinfusionGenerally re-administered in reverse order of collectionmost hemodiluted given firstunit with most clotting factors last
34 Our Patient We anticipate the possibility of 2 liters of blood loss Based on the professor’s body weight and hemoglobin, up to four units might be collected before surgery; we collect twoReplaced with 1,000 ml of hydroxyethyl starchWe use tetrastarchHis hemoglobin at the start of the procedure would be 10.0 g/dL
35 Intraoperative Cell Salvage Indicated when significant blood loss is anticipated (may be as little as 250 ml in a small patient with anemia)Full set-up when significant blood loss is likelyCollection only set-up when significant blood loss is possibleSalvage efficiency is technique dependentLow suction pressureEliminate skimmingWash spongesAvoidance of skimming and high suction pressures helps limit hemolysis and improves the efficiency of cell salvage.
36 Intraoperative Cell Salvage Relative contraindicationsBacterial contaminationSome foreign material (antibiotics, topical hemostatic agents, methyl methacrylate)MalignancyMost contraindications can be addressed through a combination of increased wash volume and filtrationTwo suctions, one for wasteLeukocyte reduction filter for bacteria and tumor cellsIrradiation for tumor?Published data have failed to show any increase in metastatic disease when cell salvage is used in surgical oncology. Definitive randomized controlled trials are unlikely since the studies would require a very large number of patients with a very high cost to conduct the study.
37 Blood Salvage and Cancer Surgery: Meta-analysis Conclusion:IBS is not inferior to traditional intraoperative allogeneic transfusion with regard to increased cancer recurrence or development of metastasisWaters et al, Transfusion doi: /j x
38 Our PatientWe decide to set up the Cell Saver in anticipation of significant blood loss.If the patient was having surgery for tumor, a leukocyte reduction filter would be usedWaste suction will be used to clear field if topical hemostatic agents used
39 Pharmacologic Agents to Limit Blood Loss Desmopressin (DDAVP, Stimate)Releases von Willebrand’s factor from endothelial cells and increases factor VIII levels0.3 mcg/kg in 50 mL over minutesCan be repeated several timesMinimal evidence of efficacy in reducing surgical blood loss except in vWD
40 Pharmacologic Agents to Limit Blood Loss Antifibrinolytic agentsAmicarTranexamic AcidInhibits clot lysis10-30 mg/kg loading dose, followed by 1-2 mg/kg/hrDecrease dose for renal insufficiencyGood evidence base: 30% reduction in blood loss in major orthopedic cases including multilevel spine and TJAStudies have shown similar reductions in blood loss when amicar is compared to tranexamic acid. However, tranexamic acid is more widely used in Europe and Canada.Br J Anaesth 2004; 93:842-58
41 Pharmacologic and Other Agents to Limit Blood Loss Topical hemostatic agentsFibrin glue (thrombin and fibrinogen concentrate)Mechanical hemostatic agents (collagen, cellulose, gelatins, etc.)Active hemostatic agentsBovine or human thrombinGelatin plus thrombinSynthetic gluesSaline-cooled radiofrequency “cautery”
42 Our Patient Surgeon plans to use topical hemostatic agents as needed This patient has a history of mild type 1 vWDPlan to administer 30 mcg of DDAVP 15 minutes before surgeryWill administer 20 mg/kg of tranexamic acid just before the start of surgery and begin an infusion of 2 mg/kg/hrWill discontinue infusion when surgery is completedSome surgeons use TXA topically
43 Day of SurgeryBoth the femoral and acetabular component require revisionUnexpected surgical bleeding is encountered
44 Intraoperative Course Four cell “salvage” runs return a total of 1,075 ml of processed blood with an average hematocrit of 55% (equivalent to about 3 units from the blood bank)The two ANH units are returned toward the end of surgery
45 Post-op Day OneThe patient’s post-op hemoglobin is 7.9 g/dL and our patient has been extubatedHe is hemodynamically stableAs planned, a fourth dose of erythropoietin is administeredThe surgeon initiates the “minimum blood volume” phlebotomy protocol to minimize blood lost for diagnostic testing
46 Strategies for Reducing Phlebotomy Blood Loss Eliminate “extra tubes”Eliminate under and over drawsIndividual nurse and phlebotomist educationSelection of testing equipment with low requisite sample volumeIncreased point-of-care testingReduce unnecessary testingReduced tube sizeSelective use of microtainers
47 Highly Conservative Phlebotomy Using a highly conservative protocol, median phlebotomy-associated blood loss (PBL) in the ICU was reduced 80% (40 ml vs. 8 ml)Mean drop in hemoglobin in ICU decreased from 2 gm/dl to 1.2 gm/dlHarber CR. Anesthesia and Intensive Care 34:4, 2006
48 If on post-op day one… What would you do? Our patient’s hemoglobin is 6.7 g/dLHis reticulocyte percentage is 7.8%His iron saturation is 13%He is walking 15 feet with assistance, but becomes short of breath and feels tiredWhat would you do?No single hemoglobin level should be used as a transfusion “trigger.” The patient is hemodynamically stable with no evidence of active bleeding, cardiac, pulmonary, or neurocognitive dysfunction. Transfusion is not indicated.
49 Post-op Iron TherapyPost-op inflammatory response creates functional iron deficiency due to increased hepcidin (our patient also has RA)Labs show decreased transferrin saturation (% saturation) below 20%Oral iron salts (e.g. ferrous sulfate) are poorly absorbed and prolong post-op ileus
50 Our PatientWe decide to administer 900 mg of low molecular weight iron dextran based on the patient’s IBW of 70 kg and hemoglobin deficit of 6 g/dLDaily folate, 1 mg for one monthDaily Vitamin C for one monthPatient is discharged home on post-op day 2 with a hemoglobin of 8.1 g/dLOne month after surgery, the patient is recovering nicely with a hemoglobin is 11.9 g/dLVitamin C seems to improve the “bioavailability” of iron in some studies.