Kay Barrera MD. Surgery Grand Rounds June 19, 2014 SUNY Downstate

Kay Barrera MD Surgery Grand Rounds June 19, 2014 SUNY Downstate

Kay Barrera MD Surgery Grand Rounds June 19, 2014 SUNY Downstate

Outline Why are we talking about this SCORE expectations When do we use MTP? Where did MTP come from? Is 1:1 the answer? Roles of TXA, Factor VIIa, PCC? Where are we going?

Why MTP? Trauma GI bleeding Post operative bleeding Retroperitoneal hemorrhage AAA rupture Obstetric / post partum bleed

Massive Transfusion Given a treatment protocol for acute blood loss, the resident can independently recall that transfusion of prbc or whole blood is indicated to replete intravascular volume and maintain end - organ perfusion.

Lane et al. Schein's Common Sense Emergency Abdominal Surgery: An Unconventional Book for Trainees and Thinking Surgeons 2010 Springer.

Massive Transfusion Defined Replacement of a patient s entire circulating blood volume (10 units) in less than 24h PRBC, Plts, FFP, Cryo Dilutional & consumptive losses of plts and clotting factors ACS Surgery Online >

When to Use MTP? Scoring systems: ABC / TASH / McLaughlin / Shock Index Need for 3 units, anticipate more Severe injury + base deficit >6 + unstable Clinical judgment Peitzman et al. THE TRAUMA MANUAL: TRAUMA AND ACUTE CARE SURGERY - 4th Ed. (2013) Lippincott Williams and WIlkins

Damage Control Resuscitation Origins in the military experience Goal early, aggressive correction of coagulopathy and metabolic derangements Three arms Permissive hypotension limited crystalloids higher ratios of plasma/platelets

Evolution of MTP Battlefield to Backyard WWII treat hemorrhagic shock with whole blood 1976 Carrico et al 1-2L of LR ( bolus ), whole blood transfusion www.downstatesurgery.org 1980s Blood banking moves to component therapy Early attitudes: 1 unit FFP for every 5 prbc (Based on exchange transfusion math for whole blood )

How 1:1 Started 1955 Krevans et al 1971 Miller et al Julius R. Krevans, M.D.; Dudley P. Jackson, M.D. HEMORRHAGIC DISORDER FOLLOWING MASSIVE WHOLE BLOOD TRANSFUSIONS JAMA. 1955;159(3):171-177 R D Miller, Coagulation defects associated with massive blood transfusions. Ann Surg. Nov 1971; 174(5): 794 801. PMCID: PMC1397560

How 1:1 Started 2003 Brohi et al / Macloud et al 25% of trauma patients are coagulopathic 2003 Hirshberg et al Computer model of dilutional coagulopathy in pelvic fractures 1:5 clearly inadequate Predicted ratio around 2:3 Showed rapid dynamics of dilution in trauma

Lessons from Iraq Borgman et al (2007) Iraq war, CSH 03-05 MTP patients Retrospective study 1:1.4 1:1 Mortality 19% Borgman MA et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13.

Battlefield to Backyard 2008- Holcomb et al Civilian population (ex-military authors) Prior 1:3 Retrospective analysis, 16 level 1 trauma centers 30d survival increased FFP:RBC, Platelet:RBC 1:2 Truncal hemorrhage Supports aiming for 1:1:1 Holcomb JB 1, et al Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. 2008 Sep;248(3):447-58. PMID 18791365

Battlefield to Backyard 2008- Holcomb et al Plasma helps with acidosis Provides fibrinogen Volume expander Holcomb JB 1, et al Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. 2008 Sep;248(3):447-58. PMID 18791365

The Evolution of 1:1 Reduction of 0.1 in RBC:FFP ratio, associated with 5.6% reduction in mortality 1:1.5 reduction in mortality, increase in ARDS Do not give 1:1 for non MTP patients Kutcher ME et al. A paradigm shift in trauma resuscitation: evaluation of evolving massive transfusion practices. JAMA Surg. 2013 Sep;148(9):834-40 PMID: 23864019 Inaba K et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg. 2010 Jun;210(6):957-65

Platelets role? Factors + Plasma probably more important? Platelets are first diluted out Based on stored whole blood that is platelet deficient ASA and Plavix use, or after 10 units of blood 1:10 ratio of apheresis platelets to blood Age of platelets is factor

Wuntwuntwun Is 1:1:1 the answer?. All retrospective studies Survival bias Time span of studies, not all patients got 1:1 Highest groups usually around 1:2 Availability bias You can t give what you don t have

MTP Massive Transfusion Protocol Kings County Hospital

4:6 Pack 4 units AB plasma, 6 units type O blood available at all times for immediate release Thawed FFP can be kept x 5 days UCSF, Stanford, University of Michigan

MTP: Logistics Cost Decreased costs $200K / year Waste Plasma Distance An important item in any MTP is identification of people who will transport laboratory and blood products Nascimento B et al Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results-guided transfusion in patients with severe trauma: a randomized feasibility trial. CMAJ. 2013 Sep 3;185(12):E583-9 PMID: 23857856 DeLoughery TG Logistics of massive transfusion Hematology Am Soc Hematol Educ Program. 2010;2010:470-3 PMID: 21239838 O'Keeffe T et al. massive transfusion protocol to decrease blood component use and costs. Arch Surg. 2008 Jul;143(7):686-90; discussion 690-1 PMID: 18645112

MTP: Logistics

Other agents Procoagulants Recombinant factor VIIa Dose 100mcg/kg, Expensive Not proven to act clinically meaninfully in major hemorrhage PCC Popular in Europe Antifibrinolytics Aprotonin Tranexamic acid (TXA) E-aminocaproic acid

#TXA http://download.thelancet.com/flatcontentassets/pdfs/txa-manga.pdf TXA the video TXA - the sound track

TXA Indications: trauma patients at risk of significant hemorrhage Antifibrinolytic, inhibits activation of plasminogen Cheap! (68-100 bucks / gram in US) Within 3 hours of major trauma

Randomized 20,000 patients, 274 hospitals, 40+ surgeries Reduction in mortality 1.5% 1g / 10 minutes + drip for 8 hours. Earlier tx the better Anti-inflammatory effects? No side effects Criticisms: SURVIVOR BIAS, ROTEM or TEG? Sites that were used, entry criteria. http://www.crash2.lshtm.ac.uk/

TXA does it MATTERS Military Application of Tranexamic Acid in Trauma Study TXA in the military population Shows mortality benefit 6.5% overall, 13.7% reduction in MTP group patients for mortality benefit improved coagulopathy profile Cons: higher rate of DVT and PTE Morrison JJ 1, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012 Feb;147(2):113-9

where are we going?

More on TXA WOMEN trial East Africa Post partum hemorrhage Head Injuries, CRASH

PROMMTT Prospective outcome measurements for massively transfused trauma patients Best early method to ID patients that will beneft from different ratios Which MTP is associated with better survival http://cetir-tmc.org/research/prommtt

PROPPR Pragmatic Randomized Optimal Platelet and Plasma Ratios 1 FFP : 1 RBC : 1 plts vs 1:2:1 Multi center http://cetir-tmc.org/research/proppr

Summary > 3units, further anticipation MTP Plasma acidic buffer, corrects coagulopathy mortality in MTP patients, harmful otherwise TXA in first three hours improves survival PROMMTT, PROPPR may define MTP ratios and protocols

True or false: Review Questions 1:1 ratios for MTP is based on Level 2 evidence True or false: is there a survival benefit to 1:1 ratios in non massively transfused patients? True or false TXA given within three hours will improve survival in MTP and non MTP patients.

References ******Dr. Asher Hirsherg graphics, references, advice 1. Lane et al. Schein's Common Sense Emergency Abdominal Surgery: An Unconventional Book for Trainees and Thinking Surgeons 2010 Springer. 2. ACS Surgery Online 3. Peitzman et al. THE TRAUMA MANUAL: TRAUMA AND ACUTE CARE SURGERY - 4th Ed. (2013) Lippincott Williams and Wilkins 4. Julius R. Krevans, M.D.; Dudley P. Jackson, M.D. HEMORRHAGIC DISORDER FOLLOWING MASSIVE WHOLE BLOOD TRANSFUSIONS JAMA. 1955;159(3):171-177 5. R D Miller, Coagulation defects associated with massive blood transfusions. Ann Surg. Nov 1971; 174(5): 794 801. PMCID: PMC1397560 6. Borgman MA et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13. 7. Holcomb JB 1, et al Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. 2008 Sep;248(3):447-58. PMID 18791365 8. Kutcher ME et al. A paradigm shift in trauma resuscitation: evaluation of evolving massive transfusion practices. JAMA Surg. 2013 Sep;148(9):834-40 PMID: 23864019 9. Inaba K et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg. 2010 Jun;210(6):957-65 10. CRASH 2 collaborators Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial The Lancet 3 July 2010 (Volume 376 Issue 9734 Pages 23-32. 11. Morrison JJ 1, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012 Feb;147(2):113-9