1:1:1 Ratio of Massive Transfusion Program # Wednesday, December 12, :00 pm-3:30 pm (ET) ~ 7:00 pm-8:30 pm (GMT)

Transcription

1 1:1:1 Ratio of Massive Transfusion Program # Wednesday, December 12, :00 pm-3:30 pm (ET) ~ 7:00 pm-8:30 pm (GMT) Patients suffering from traumatic injuries require aggressive treatment. Massive blood loss may be apparent but the mechanism to stop the bleeding may not. The use of a Massive Transfusion Protocol (MTP) is necessary for these patients in order to stabilize the patient and stop the bleeding. But what is the appropriate ratio of blood products needed for these patients? This program will look at the use of a 1:1:1 ratio of blood products and the benefits of this ratio. Objectives: Define what determines the need for a MTP to be initiated. Assess how much blood should be available for MTP patients. Discuss if the use of a 1:1:1 ratio of blood products is appropriate or necessary. Director/Moderator: Shelvi McFadden, MLS(ASCP) Transfusion Service Supervisor Shands Jacksonville Medical Center Faculty: John Holcomb, MD, FACS Professor and Vice Chair of Surgery University of Texas Health Science Center

2 The Accreditation Council for Continuing Medical Education (ACCME) is the governing body that accredits AABB to provide continuing medical education credits for physicians. In accordance with the ACCME Standards for Commercial Support, all faculty for this event have signed a conflict of interest form in which they have disclosed any significant financial interests or other relationships with the industry relative to the topics they will discuss during this program. Such disclosure allows you to better evaluate the objectivity of the information presented in the lectures. Please report any undisclosed conflict of interest you may perceive on the evaluation form. Thank You. Below please see the disclosures for this program: Director/Moderator: Shelvi McFadden, MLS(ASCP) Transfusion Service Supervisor Shands Jacksonville Medical Center Disclosures: No Disclosures Given Faculty: John Holcomb, MD, FACS Professor and Vice Chair of Surgery University of Texas Health Science Center Disclosures: Nothing to Disclose Name/Role in Content Planning Disclosure Nature of relationship Manufacturer/Provider Kristi Williams, planning committee member Michele Anastasi, planning committee member Meghan Delaney, planning committee member Dina Hannah, planning committee member Jerry Holmberg, planning committee member Monica LaSarre, planning committee member Veronica Lewis, planning committee member Shelvi McFadden, planning committee member Laurie McGraw, planning committee member Gail Moskowitz, planning committee member Elizabeth O'Neill, planning committee member Sharon Moffett, planning committee member, AABB staff Lauren Rohde, planning committee member, AABB staff none none none none yes none none none none none none none none Employee US Department of Health and Human Services

3 Accessing your Continuing Education Credits Online! 1. Log into the Live Learning Center from the website 2. Go to Professional Development 3. Click on red link that says AABB Live Learning Center on the left side of the page 4. Click on red link that says AABB Live Learning Center in the center of the page 5. Click the My Account link at the top of the page. 6. Log in using your address and password. 7. Click on the link that says My Transcripts 8. Go to the Select Conference drop down menu and select 2012 Audioconference Series 9. Choose the appropriate audioconference title.

4 Damage Control Resuscitation Today: A New Paradigm John B. Holcomb, MD, FACS Professor and Vice Chair of Surgery University of Texas Health Science Center, Houston, TX 1 Texas Trauma Institute Houston, TX 2 Injury Statistics World wide = 5 million deaths per year 10% of global deaths are due to injury Cost of $518 billion annually United States = 29 million people injured/yr 10% of US population 747 every day Leading cause of death age 1-44 Leading cause of life years lost 1

5 Memorial Hermann-TMC and UT Health Trauma Volume Update slide 4 UTHSC-Houston Trauma admissions = 36,028 and 2394 deaths = 6.6% Early deaths ( 24 hrs) = 1398 or 58% 30 % hrs = 58% 72 hrs = 72% 6 days = 92% 30 days = 97% Deaths from day = 68/2394 = 3% 5 Coagulopathy of Trauma..Balance.. Majority (90%) are Pro-thrombotic Need anticoagulation DVT / PE Minority (<5%) at risk of MT Bleeding / Death Coagulopathy of trauma is dynamic 6 2

6 Bottom Line Up Front Crystalloid resuscitation increase blood loss, transfusion requirements and death Balanced blood product resuscitation decreases blood loss, transfusion requirements and improves survival Adjuncts are promising and data are evolving Time is critical 7 How to Resuscitate? Its not just raise the BP Not just the hole in the blood vessel that needs rapid suture Reverse the systemic endothelial injury Reverse permeability Prevent edema Repair the endothelium Dampen the systemic inflammatory response Prevent and Reverse coagulopathy Time is important 8 Shock, 2006 McClelland RN, Shires GT, Baxter CR, Coln CD, Carrico CJ. Balanced salt solution in the treatment of hemorrhagic shock. JAMA FD Moore, Shires G. Moderation. Anes & Analg Bickell WH, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. NEJM Rhee et al. Human neutrophil activation and increased adhesion by various resuscitation fluids. Crit Care Med Brandstrup B, et al. Effects of IV fluid restriction on postop complications: a comparison of two perioperative fluid regimens. Annals of Surg, NHLBI ARDS NET Clinical Trials Network; Wiedemann HP, et al. Comparison of two fluid-management strategies in acute lung injury. NEJM

7 Prospective, randomized, blinded 66 patients undergoing elective AAA NS vs LR administered to keep CVP or PCWP within 10% of baseline Blood product use standardized Anesth Analg Increased acidosis Gave less total blood products 10 J Trauma 2011 ED crystalloid volume replacement of 1.5 L or more was an independent risk factor for mortality. 11 J Trauma

8 Trans 2011 These data suggest that blood products as initial resuscitation fluids reduced blood loss from a noncompressible injury compared to Hextend or LR. 13 Chest, 1988 Chest, 1992 J Trauma, Typical 24 hour Resuscitation THEN 20 liters of LR 15 RBCs 5 FFP 0 platelets NOW 3-5 liters of LR 7 RBCs 6 FFP 1 platelets Associated with decreased edema, MOF and improved survival 15 5

9 Arch Surg % of admissions received a blood transfusion within 6 hours of admission Overall mortality was 25% 94% of hemorrhagic deaths occurred within 24 hours the median time to hemorrhagic death was 2.6 hours, interquartile range, hours 16 Small numbers, but big mortality There were 34,362 trauma admissions in 10 centers over 58 weeks 12,560 (36%) highest level activations 1245 (10%) were transfused within 6 hours 905 (7%) received a transfusion of 3 RBCs 25% mortality 17 PROMMTT plasma:rbc Hem death at 2.6 hrs 18 6

10 PROMMTT platelets:rbcs Hem death at 2.6 hrs 19 PROMMTT In rapidly bleeding trauma patients, inadequate transfusion of plasma and platelets was associated with early death. However, the actual transfusion of blood products is a complicated balance between; 1. rapid recognition of need 2. ordering of appropriate products 3. product availability in the blood bank 4. obtaining those products quickly 5. and appropriate infusion. 20 PROMMTT These prospective data suggest that the association between earlier and higher ratios of plasma and platelets and decreased in-hospital mortality is concentrated in the first 6 hours. in patients with substantial bleeding. 1:1:1 is superior to 1:1:2 21 7

11 The Lethal Triad before 2003 Acidosis Death Hypothermia Coagulopathy Brohi K, et al. J Trauma, MacLeod J, et al. J Trauma J Trauma, Oct J Trauma, Derangements in coagulation occur rapidly after trauma even after adjusting for ISS By the time of arrival at the ED, 1/3 of trauma patients had a coagulopathy associated with a poor outcome 24 8

12 Annals of Surgery, May Which one to use, start, how much, stop?? 26 Component Therapy Component Therapy: 1U PRBC + 1U PLT + 1U FFP + 1 U cryo 680 COLD ml Hct 29% Plt 80K Coag factors 65% of initial concentration 1000 mg Fibrinogen Armand & Hess, Transfusion Med. Rev., 2003 WWB: 500 ml Warm Hct: 38-50% Plt: K Coag: 100% 1000 mg Fibrinogen 9

13 J Trauma, Rapid progress in trauma care occurs during a war. Damage control resuscitation addresses diagnosis and treatment of the entire lethal triad immediately upon admission. 29 DCR components Stop bleeding Hypotensive resuscitation Minimize crystalloid Use plasma to resuscitate patients Increased platelet use Reverse hypothermia and acidosis Hemostatic adjuncts 30 10

14 Typical 24 hour Resuscitation THEN 20 liters of LR 15 RBCs 5 FFP 0 platelets NOW 3-5 liters of LR 7 RBCs 6 FFP 1 platelets Associated with decreased edema, MOF and improved survival History is Important 33 11

15 How did we get in the current situation? What we transfuse is important When was the paper published Composition of the product Relevance of the conclusion to today s practice Why do you order LR or NS and RBCs? 34 Arch Surg, % TBW = 4-5 liters 35 Lactated Ringers is used to replace interstitial fluid and to support the intravascular volume until type specific cross matched whole blood is available. LR at a very rapid rate, ml over 45 minutes until whole blood is available. Observe if the patient is a responder or non responder Base further whole blood transfusion on the patients response Seems very reasonable and sounds very familiar 12

16 Counts RB, Haisch C, Simon TL, Maxwell NG, Heimbach DM, Carrico CJ Hemostasis in massively transfused trauma patients. Ann Surg. Ann Surg 1979 Twenty-seven patients requiring massive transfusions were studied prospectively to determine whether administration of stored, modified whole blood induced a primary disorder of hemostasis evidenced by generalized microvascular oozing. The only labile clotting factors (storage) are V and VIII. Fibrinogen and the vitamin K-dependent factors are preserved in blood stored for 21 days at levels greater than 60% in fresh blood or fresh frozen plasma. Plasma transfusion is not needed to provide clotting factors as a supplement for whole blood transfusions in patients who are bleeding. to do is unnecessary and wasteful 37 Surgery, patients, 28% mortality 21 units of blood, 1262 ml FFP (4:1) 19 liters of crystalloid No indication for prophylactic platelet transfusion unless medical bleeding No comparison groups Ann Surg 1986 Only randomized study in transfusion Platelets vs plasma But a small study ( n = 33) Did not study ratios Used modified whole blood and waited until 12 units of MWB before transfusing platelets No effect of prophylactic platelets Recommendation: wait until MV bleeding occurs then treat with platelets 39 13

17 Transfusion in Feliciano, Mattox and Moore, 6 th edition, 2008 Recommends platelets and FFP based on lab tests While you wait another 20% of your MT patients die 40 What is the Lesson? 78 patients from 3 small single center studies using products no longer available Read the literature Evaluate the data Question everything Don t passively accept the status quo Do research 41 Whole bld 21 days 1945 Plasma Components 35 days 1979 Components 35 days 1988 Components 42 days 1995 Future 56 days? 42 14

18 Mortality Component Therapy Little quality clinical outcome data as we moved from whole blood to components Plasma removed from initial components Designed largely for extension of shelf life vs outcome of individual patients Do they really work as advertised? They likely work very well for patients not in shock who need a few units Vast majority of patients 43 J Trauma, % % , n = 252 P < % 162 (Low) 1:8 (Medium) 1:2.5 (High) 1: Ann Surg 2008 Multicenter (16) Retrospective Massive Transfusion Study 12 months data collection 30,000 admissions and 11,650 transfused 466 MT s 45 15

19 Increased Plasma and Platelet to RBC Ratios Improves Outcome in 466 Massively Transfused Civilian Trauma Patients 11,650 transfused and 30,000 admissions 46 Mortality vs mean FFP/RBC ratio by Center and Variability 47 Survival and Cause of Death 48 16

20 24 hour Kaplan-Meier day Kaplan-Meier 50 Transfusion,

21 JACS hrs 24 hrs 52 Add Holcomb platelet study J Trauma, 2011 N = 643 low (1:20), medium (1:2), and high (1:1) 53 Transfusion,

22 J Trauma 2009 MT protocol implemented and compared to :2 RBC:FFP and 5:1 RBC:Platelets 141 vs 125 MT patients MT protocol group was sicker MOF lower, 9 vs 20%, p < day survival higher 57 vs 38%, p < 0.01 Difference attributed to rapid implementation plasma and platelets, resulting in earlier transfusion of plasma and platelets 55 > 20 papers >2000 patients Vox San J Trauma, , n = 1123, DCL = % DCL rate 15 L 15 RBCs 13 FFP 57 19

23 Ann of Surg, vs DCR in DCL: DCR patients received less, (p<0.05). crystalloids (14 L vs. 5 L), RBC (13 U vs. 7 U), plasma (11 U vs. 8 U) platelets (6 U vs. 0 U) ALI, AKI, MOF all lower in DCR patients 24-hour and 30-day survival was higher in DCR (88% vs. 97%, p=0.01 and 76% vs. 86%, p=0.03). MTs in the DCL population decreased from 67% to 43% (p<0.01) In severely injured patients who underwent DCL; DCR was associated with both decreased blood product use and improved survival. 59 J Trauma 2009 Very important paper, not only for this topic, but all uncontrolled studies They lived long enough to receive a treatment, not that the treatment caused them to live longer However at UAB, they don t give plasma early Median of 18 min vs 93 (RBC vs plasma administration) 60 20

24 J Trauma 2009 J Trauma Survival Bias Real when products are in the Blood Bank Removed when products are in the ED Multiple steps involved, including early ordering, availability of thawed plasma, rapid delivery, balanced infusion 62 How do you make early blood products happen? Use blood products early and as a primary resuscitation fluid O- RBCs in the ED AB or A plasma in the ED Platelets in the ED? Prehospital?? 63 21

25 Transfusion Cotton BA et al. Accepted, Arch Surg, 2012 We demonstrated that implementation of a ED-TP protocol expedites transfusion of plasma to severely injured patients. Infusion time is now within 5 minutes This approach was associated with a reduction in overall blood product use and improved survival. 65 Plasma for everyone? Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intensive care unit: benefit or harm? Crit Care Med Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on PT and bleeding in patients with mild coagulation abnormalities. Transfusion

26 Evidence based guidelines Transfusion transmitted infections TRALI WBC reduction Avoiding pooled products IT to decrease admin errors Risk vs Benefit 67 All the retrospective studies Whole Blood vs Components Study Frozen Blood vs Stored Blood 68 J Trauma,

27 J Trauma 2011 J Trauma 2012 Ann Surg How we use TEG 71 R-TEG Graphical Display in the ED We no longer send PT / PTT / INR, fibrinogen and platelet counts 24

28 So what do we do - today Identify patients who need resuscitation Prehospital and hospital Use blood products, not crystalloid or artificial colloids Transfuse in a balanced fashion, starting with the first units Platelets early When the rate of transfusion slows, transition to TEG driven 73 Concept Not rigidly ratio driven Not rigidly TEG (or ROTEM) driven Incorporates the elements of time and logistics and personnel specific to our site 74 How does plasma work? Is it all the same? Replace lost or consumed coagulation proteins? Stabilize the endothelium? Just a better colloid? Need some mechanistic work here 75 25

29 Fold decrease in permeability above control J Trauma 2010 It is possible that the thousands of proteins in FFP promote vascular stability through regulation of critical junction proteins. Compromise of EC junctions could lead to a number of deleterious effects: barrier dysfunction, interstitial edema, tissue hypoxia, inflammatory cell infiltration, detached pericytes, extracellular matrix breakdown, apoptosis and exposed subendothelium. We suggest a possible beneficial effect of FFP on hemostasis at the EC level, as opposed to the traditional view of FFP as only a source of clotting factors. 76 Pulmonary Endothelial Cell Permeability 10 Day 0 8 Day 5 6 Day 10 4 LR 2 LP % 30% 5% 100% 30% 5% 100% 30% 5% 100% 30% 5% 100% 30% 5% Findings: 1. Plasma and LP are both Protective against EC permeability 2. LR has no protective effects on EC permeability 3. The protective effects of plasma diminish with time Anes & Analg, 2011 The glycocalyx is a ubiquitous barrier that protects the underlying endothelium and prevents injurious neutrophilendothelial interaction. A C A = baseline B= shock C = LR resus C = Plasma resus B D 78 26

30 79 In vitro and In Vivo Studies We must understand the blood products we are using now Establish a mechanistic basis for current products and then rational design for improved, new products Avoid the mistakes of the past Combine the power of mechanistic information, quality clinical data, predictive algorithms and small computers 80 Back to the Future Lyophilized Plasma Resuscitation 81 27

31 Prehospital and Hospital No distinction Should be a seemless continuum What works in the hospital should be used prehospital 82 New Equipment/Concepts on Helicopters Tourniquets Hemostatic Dressings Femoral compression device Ultrasound Smart vital signs monitor I Stat laboratory device Fluid warmers RBCs and Plasma 83 RBC and FFP on Helicopters 12 months 4 helicopters 2 units O- and 2 units thawed AB plasma Indications for transfusion same as in the ED 108 patients 98 trauma 90% continued receiving products in the ED 84 28

32 J Trauma 2011 In the next evolution of trauma transfusion practice, it is exciting to consider the real logistical and possible clinical benefits of exclusively using dried products such as plasma, platelets, fibrinogen, and RBCs to resuscitate trauma patients. 85 The Future Dried / Lyophilized Components Lyophilized Fibrinogen Used for trauma patients in Austria Approved in US Frozen, FD platelets or Lyophilized Platelets human studies and animal trials (LP) European countries in Afghanistan Dried plasma animal studies Human trials Approved in many EU countries, used in Afghanistan RBCs Stem cell derived-darpa lyophilized RBC s Various individual recombinant coagulation proteins 86 Plasma Studies Excellent baseline standard of care from PROMMTT and PROPPR Ongoing prehospital plasma study by DoD New more logistically favorable products need rapid preclinical evaluation and then appropriate human studies Must be dried, storage for 2 years at ambient temp, rapid mixed and universal donor 87 29

33 Regulatory Pathway Clear pathway Use Trauma patients Largest # of big bleeding patients Studies can be done in months at centers. 88 Mass casualty Extend concepts of individual care For overwhelming, use minimal acceptable care Triage of time, personnel, supplies Stockpile dried products Rotate out into clinical practice so clinicians are familiar and will use them during a mass casualty situation 89 Summary Uncontrolled Hemorrhage is a major problem Limit crystalloid, use more plasma and platelets Predictive models are here Must start components earlier Place blood products in the ED Do the preclinical and human studies Improved study design and analysis Mechanistic studies will allow more focused tx 90 30

34 Summary Use physiology (not tradition) to drive diagnosis and interventions Don t make the presenting problems worse with an iatrogenic resuscitation injury. Give a balanced resuscitation Accept known risks and benefits Work collaboratively Understand basic and clinical science Use new diagnostic tools Must do large prospective and randomized trauma studies 91 Thank You 31

35 Upcoming Audioconference: CDC's Hemovigilance Module of the National Healthcare Safety Network: How Your Hospital Can Monitor Transfusion-related Adverse Events December 19, :00 pm to 3:30 pm (ET); 7:00 pm to 8:30 pm (GMT) Program # CDC representatives will conduct a live demonstration of the National Healthcare Safety Network Hemovigilance Module, a surveillance system available free to US Healthcare facilities to monitor transfusion-related adverse reactions and process incidents. *This audioconference will utilize Webinar software. Please make sure you will have Internet access during the presentation.* Objectives: Demonstrate major features of the Hemovigilance Module of the National Healthcare Safety Network. Explain how CDC will protect the hemovigilance data received from facilities. Explain how participating facilities can use their own data for process improvements. Describe the steps necessary for facilities to join NHSN. Intended Audience: Physicians, Technologists, Nurses, Managers/Supervisors, Perfusionists Teaching Level: Intermediate Director/Moderator/Speaker: Barbee Whitaker, PhD Director, Center for Data and Special Programs AABB Faculty: Koo-Whang Chung, MPH Public Health Analyst Emergint Technologies

36 AABB would like to thank the members of the AABB Distance Learning Program Unit for their assistance in developing these programs: 2012 Distance Learning Program Unit CHAIR Kristi Williams, MT(ASCP)SBB, CQA, CQIA(ASQ) Manager, Biomedical Headquarters IRL Operational Support, American Red Cross Washington, IL Michele Anastasi BS,MT(ASCP)SBB Night Lab Supervisor, Hines VA Hospital Hines, IL Colleen Aronson, MT(ASCP)SBB Quality Programs Coordinator, Northshore University Healthsystem Evanston, IL Meghan Delaney, MD Physician, Puget Sound Blood Center Seattle, WA Dina Hannah MBA/HCM, MT(ASCP) H, SBB, CIPP VP, Asst. Director of Quality and Compliance, ARUP Blood Services Salt Lake City, UT Monica LaSarre MT(ASCP)SBB Manager, Reference Laboratory, Bonfils Blood Center Denver, CO Veronica Lewis, MS, MT(ASCP)SBB Assistant Professor / Director, SBB Certificate Program, Rush University Chicago, IL Shelvi McFadden, MT(ASCP) Transfusion Service Supervisor, Shands Jacksonville Medical Center Jacksonsville, FL Sharon Moffett, CAE Director of Education and Professional Development, AABB Bethesda, MD Gail Moskowitz, MD Independent Consultant New York, NY Elizabeth O Neill, MD Physician, American Red Cross Blood Services Dedham, MA Lauren Rohde Programs Manager, AABB Bethesda, MD Jayanna Slayten, MS, MT(ASCP)SBB Reference Laboratory Supervisor, Indiana Blood Center Indianapolis, IN