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Resuscitation from Massive Hemorrhage & Development of the MTP: Perspective of an Obstetrical Anesthesiologist Alan I. Frankfurt, MD Partner, ATLAS Anesthesia.

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Presentation on theme: "Resuscitation from Massive Hemorrhage & Development of the MTP: Perspective of an Obstetrical Anesthesiologist Alan I. Frankfurt, MD Partner, ATLAS Anesthesia."— Presentation transcript:

1 Resuscitation from Massive Hemorrhage & Development of the MTP: Perspective of an Obstetrical Anesthesiologist Alan I. Frankfurt, MD Partner, ATLAS Anesthesia Irving, Texas Department of Anesthesiology TH Dallas-Presbyterian Hospital 1 From the ED to the battlefield and back to the ED/bedside

2 Learning Objectives  History lesson  Incidence of MT  DCR & “5 H’s”  Coagulopathy and morbidity in hemorrhagic shock  Lethal triad  Evolution of the MTP: responding to an iatrogenic coagulopathy  Maryland Shock Trauma  Somalia & Iraq/Afghanistan  1:1:1 vs. 1:1:2-it’s a math thing  PROMMTT  PROPPRR  Thoughts for your day to day practice in the ED. Alan I. Frankfurt, MD 2

3 HISTORY OF WARTIME PREHOSPITAL/ER SHOCK RESUSCITATION WW I/WW II Vietnam Korea OIF/OEF 50 years of Plasma, Albumin and Whole Blood 40 years of Crystalloid/ Clear Fluids & WB: 1.3rd space resuscitation 2.Fractionation of WB Forward to the past( DCR): 1.Early plasma 2.”WB” equivalent 3.FWWB

4 Damage Control Resuscitation “5 H’s” Hemorrhage control ▫OR timely fashion  Definitive solution to bleeding is in the OR/IR Hypotensive resuscitation ▫Systolic BP=80-90 torr  “Tolerate” shock vs. Popping clots Hemostatic resuscitation ▫Blood products early and often: Plasma  Prevention of coagulopathy  Dilution  ACoTS ▫Minimize crystalloid administration Homeostasis ▫Hypothermia ▫Acidosis Hypnosis: having our cake and eating it too ▫DCA  Vasoconstriction Vasorelaxed 4

5 Elements of hemostatic resuscitation, and level of evidence in support: R. Dutton; BJA 2012, Vol109 no. suppl 1 i39 RecommendationsEvidence  Expedited anatomic control in OR Strong; widely accepted  Deliberate (permissive) hypotension Several prospective trials; widely accepted Early support of coagulation  Antifibrinolytic therapyOne large prospective trial, several smaller studies; emerging standard  Early use of early plasma and platelets in massively bleeding patients 1:1:1 Controversial; variable application in clinical practice (PROMMTT); PROPPR trial  Vasodilation with anesthetic agents aka (DCA) Theory only. Minimal clinical data Alan I. Frankfurt, MD 5

6 Hypotensive Resuscitation A Historical Perspective Alan I. Frankfurt, MD 6

7 Hypotensive Resuscitation: A Balancing Act Alan I. Frankfurt, MD 7 Permissive ischemia Tolerating short period of hypotension Vs. Popping a clot Minimize the risk of increased bleeding

8 Blood Pressure at which Rebleeding Occurs after Resuscitation in Swine with Aortic Injury Jill L. Sondeen, PhD J of Trauma 54: (5) May Supp 2003 Reproducible blood pressure at which rebleeding occurred in test animals. ▫Systolic 94 mmHG ▫Diastolic 45 mmHG ▫MAP 64 mmHG  Similar to resuscitation pressures suggested by Drs. Cannon (WW1) and Beecher (WW2), respectively.  Stern SA; Ann Emerg Med 1993 Feb; 22: 155  Burris D.; J Trauma 1999;46:  Stern SA; Prehosp Emerg Care. 2002;6:81-91 Standard component of DCR Alan I. Frankfurt, MD 8 Keep the SBP torr until the bleeding is controlled.

9 73,000 foot view of Hemorrhage Resuscitation: Keeping the Resuscitation Fluids Administered to a Hemorrhaging Patient, Looking Like Blood Coming Out  Early blood product administration (MTP)  Early Plasma  ? Cryoprecipitate & Platelets  Minimize IV crystalloids  Avoid coagulopathy Alan I. Frankfurt, MD 9

10 Basics How much do young healthy trauma patients bleed before the patient demonstrates changes in routine vital signs (BP, P, RR, LOC). Do routine vital signs reflect EBL & occult shock? If not, what should we be following? What kills you when you “bleed to death”? Alan I. Frankfurt, MD 10

11 Class EBL- estimated blood loss. %EBV Lost Pulse Rate Blood Pressure Mental Status Class I<750cc<15%<100 Normal Slightly anxious Class II cc15-30%>100 Normal Mildly anxious Class III Life threatening 1500(2000)cc 30-40% >120 Weak or intermittent Radial pulse DecreaseConfused Class IV Life Threatening >2000cc40-50%>140 Absent radial pulse. Decrease Lethargic, Confused, Unconscious ACS ATLS Clinical Signs Associated with Blood Loss: 11 Alan I. Frankfurt, MD Loss of Effective Compensatio n Loss of Effective Compensatio n

12 ATLS Clinical Signs Associated with Blood Loss Alan I. Frankfurt, MD 12

13 Classification of Shock Using ED Admission Arterial Base Deficit Values Defined by JW Davis, MD et al. Alan I. Frankfurt, MD 13 Admission Base Deficit Predicts Transfusion Requirements and Risk of Complications James W. Davis, MD; Jour of Trauma, Vol. 3, No. 5: 769

14 Questioning the validity of the ATLS classification in hypovolemic shock: the role of (venous) BD/Lactate Alan I. Frankfurt, MD

15 Alan I. Frankfurt, MD 15 Mutschler et al. Critical Care 2013, 17:R42

16 Alan I. Frankfurt, MD 16 Mutschler et al. Critical Care 2013, 17:R42

17 Alan I. Frankfurt, MD 17 Mutschler et al. Critical Care 2013, 17:R42

18 Hemorrhagic death is the result of systemic vascular collapse Alan I. Frankfurt, MD 18

19 40% 19 MAP EBV~5000cc/70 kg person Venoconstriction Arterial constriction Vascular capacitance= X3 EBV Increasing blood loss Endothelial ischemia & Acidosis pH<7.2 Loss of vascular reactivity Catecholamines Systemic vasodilatation Vascular collapse 10% 20%30% 50-60% Systemic vascular collapse Baseline vascular tone Baseline vascular tone

20 Pathway to Vascular Collapse and Decompensated Shock Alan I. Frankfurt, MD 20

21 Lethal Triad of Trauma: Marker of Physiologic Exhaustion Alan I. Frankfurt, MD 21 Coagulopathy INR Acidosis Hypothermia Best single live/die predictor in trauma & hemorrhage patients.

22 The Lethal Triad Alan I. Frankfurt, MD 22 Massive Hemorrhage Massive Hemorrhage

23 The Lethal Triad Drives Resuscitation Efforts Hemorrhage control (stop the bleeding) ▫Operating room ▫Interventional radiology Volume administration (fill the tank) ▫Preload/Cardiac output/MAP CaO2 (oxygen carrying capacity) ▫Hg x SpO2 x K  pRBC Coagulation (make clots) ▫MTP  FFP  Cryoprecipitate  Platelets  Antifibrinolytics Homeostasis (keep the patient warm) ▫Normal physiologic environment  Hypothermia  Acidosis  Calcium Alan I. Frankfurt, MD 23 Damage Control Resuscitation

24 Damage Control Alan I. Frankfurt, MD 24

25 Damage Control Resuscitation Resuscitative measures that are taken to prevent physiologic exhaustion (lethal triad) and patient death. Alan I. Frankfurt, MD 25

26 Damage Control Resuscitation “5 H’s” Hemorrhage control ▫OR timely fashion Hypotensive resuscitation ▫Systolic BP=80 torr  Ischemia vs. Popping a clot Hemostatic resuscitation ▫Early plasma administration  Fibrinogen/EG ▫Minimize crystalloid administration ▫MTP  1:1:1:(1) ratio  riaSTAP  TXA  rF7 ▫RBC  Hct 35-40% ▫Platelets  >100,000 Homeostasis ▫Hypothermia ▫Acidosis ▫Ionized calcium ▫Labs  INR/TEG  ABG  Base deficit  Lactate  CBC/Chem 7/platelets  Fibrinogen Hypnosis: having our cake and eating it too ▫DCA  Hypotension  Vasoconstriction/Hypovole mia  Hypotension  Vasodilatation/Euvolemia 26

27 Massive Transfusion Protocols Alan I. Frankfurt, MD 27

28 Shipment #pRBCsPlasmaPlatelets apheresis Role of : rF7a vs. TXA 28 Alan I. Frankfurt, MD Massive Transfusion Protocol Version 1.0 Composition and Implementation MTP initiation: Bleeding and in hypovolemic shock Not sure what is bleeding. How long it will take to stop the bleeding. What it is going to take to stop the bleeding. When you’re bleeding too fast to wait for the labs. MTP initiation: Bleeding and in hypovolemic shock Not sure what is bleeding. How long it will take to stop the bleeding. What it is going to take to stop the bleeding. When you’re bleeding too fast to wait for the labs.

29 Massive Transfusion Protocol Version 2.0 (Modify based upon severity of blood loss & institutional capabilities) 29 Last in, first out: <14 days old Early plasma Day 1-3 Plasma ratio vs. Plasma deficit Fibrinogen vWB F8 F13 Fibronectin Europe vs. USA Lyophilized fibrinogen Fibrinogen is the first factor to reach critically low levels during massive bleeding Is there a role for rF7 in massive hemorrhage? Anti- fibrinolytic

30 Advanced Trauma Life Support (ATLS) Alan I. Frankfurt, MD 30

31 Advanced Trauma Life Support (ATLS) Hemorrhage resuscitation circa1980 Crystalloid infusion: ▫Dilution clotting factors ▫Does not carry oxygen ▫Hypothermia ▫Worsening of bleeding pRBC administration: ▫Signs of shock Playing catch up with coagulation ▫FFP/Cryoprecipitate  Driven by PT/PTT lab test  20” lab result turn around  20 minutes to dethaw ▫Continued crystalloid fluid administration and pRBC ▫Platelets 31 Iatrogenic driven coagulopathy

32 Bloody Vicious Cycle of Biblical Proportion Alan I. Frankfurt, MD 32

33 Breaking the Bloody Vicious Cycle Damage Control Resuscitation“5 H’s” Hemorrhage control ▫OR timely fashion  Definitive hemorrhage control Hypotensive resuscitation ▫Systolic BP=80-90 torr  “Tolerate” shock vs. Popping clots Hemostatic resuscitation ▫Blood products early and often: Plasma  Prevention of coagulopathy ▫Minimize crystalloid administration Homeostasis ▫Hypothermia ▫Acidosis 33 Year 2000 (limited trauma centers) DCS DCR: “WB equivalent” Early plasma Year 2000 (limited trauma centers) DCS DCR: “WB equivalent” Early plasma

34 34 Is There a Role for Whole Blood in Civilian Hemorrhage Resuscitation? Keeping Fluids Going Into our Patients Looking Like Blood Coming Out During a Hemorrhage Resuscitation

35 Civilian Use of Whole Blood is Limited Military: (Fresh Warm) Whole Blood ▫Warm: C* ▫Fresh if < 24 hours old ▫Walking blood bank  Pre-tested Civilian: Whole Blood ▫Cold: 1-4C* ▫Formal testing for transmissible disease.  72 hours ▫Licensed for 21 days ▫Difficult to obtain from blood centers  Fractionation of WB ▫Efficient use of blood product ▫Financial Alan I. Frankfurt, MD 35 ≠

36 Is the MTP (1:1:1) the Modern Day Whole Blood Equivalent: 36 Crystalloid fluid ▫Poor volume expander ▫Carries no oxygen, coagulation factors What if we administer the fractionated parts of WB as a 1:1(:1) ratio? ▫Volume ▫Oxygen delivery ▫Coagulation factors

37 Origin of the (Civilian) MTP 1:1:1 transfusion ratio John Hess, MD; Richard Dutton, MD: From ISR to Maryland STU 2000 Transfusion Vol. 44, Issue 6 pp , June 2004 Blood transfusion rates in the care of acute trauma John J. Como, Richard Dutton, Thomas M. Scalea, Bennette B. Edelman, John R. Hess Transfus Med Rev. 2003; 17: Treating coagulopathy in trauma patients Armand R., Hess JR Alan I. Frankfurt, MD 37

38 Origin of the MTP 1:1:1 Ratio Maryland Shock Trauma, Baltimore Md. Early plasma administration ▫Dr. Como et al.(Transfusion 2004);  “Blood transfusion rates in the care of acute trauma”  8% (479/5645 trauma admissions 2000) received RBC transfusion  3% > 10U RBC/24 hours ▫90% ultimately received plasma  5645 trauma admissions to Shock Trauma Center in 2000  5219 units of RBC  5226 units of FFP  RBC ED  FFP ICU  Lack of immediate availability of plasma 38 Alan I. Frankfurt, MD 1:1 ratio

39 Birth of the Massive Transfusion Protocol (MTP) ▫Question:  “Are we using FFP in the ICU to rescue an iatrogenic (ATLS) induced coagulopathy from the ED/OR resuscitation?”  “What if we gave the FFP at the same time as the pRBC in patients with massive hemorrhage?” (personal communication, Richard Dutton, MD) ▫Drs. Dutton, Hess & Holcomb  1:1 RBC/FFP in ED  Baltimore, Md  Bagdad, Iraq 2005 Alan I. Frankfurt, MD 39

40 Is the Massive Transfusion Protocol 1:1:1 ratio the WB equivalent? (Kinda) 1 unit pRBC: 1 unit FFP: = 1 unit (apheresis) platelets 1 unit “whole blood” equivalent? 1 unit “whole blood” equivalent? 40

41 MTP 1:1:1 “Hemotherapy induced hemodilution” TempHctPlateletsCoagulation Factor % FibrinogenAmount of anticoagulant and additives Whole Blood 500cc WFWB 37* C38- 50% 150,000 to 400, %1500 mg63cc Component Therapy 680cc 1 unit: PRBC, FFP, Platelet -30-0*C29%88,00065%950 mg205cc Alan I. Frankfurt, MD 41

42 MTP 1:1:1 “Hemotherapy induced hemodilution” TempHctPlateletsCoagulation Factor % FibrinogenAmount of anticoagulant and additives Whole Blood 500cc WFWB 37* C38- 50% 150,000 to 400, %1500 mg63cc Component Therapy 680cc 1U: PRBC, FFP, Platelet -30-0*C29% (10% ) 26% 88,000 (30%) 55,000 65%750 mg205cc Alan I. Frankfurt, MD 42

43 MTP 1:1:2 “Hemotherapy induced hemodilution” TempHctPlateletsCoagulation Factor % FibrinogenAmount of anticoagulant and additives Whole Blood 500cc WFWB 37* C38- 50% 150,000 to 400, %1500 mg63cc Component Therapy 680cc 2PRBC, 1FFP, 1Platelet -30-0*C29%88,00065%750 mg205cc Alan I. Frankfurt, MD 43 52%55,00040% Storage related losses 36%37,00052% Any crystalloid administered will further dilute all 3 blood components. 26%55,000 65% 1:1:1 1:1:2

44 PROPPR Trial: JAMA 2015, 313(5): Study Question In patients with severe trauma and predicted to require massive transfusion, does the use of a transfusion protocol using a 1:1:1 ratio of plasma to platelets to red blood cells (RBCs) compared to 1:1:2 improve mortality? Alan I. Frankfurt, MD 44

45 PROPPR Trial: Results 24 hour/30 day all cause mortality ▫No difference between 1:1:1 vs 1:1:2 Reduced mortality in 1:1:1 group from exsanguination in the first 24 hours. The Kaplan-Meier survival curves for a 3 hour endpoint: ▫Statistically significant mortality difference between the two groups.  This was not one of the allowed primary outcomes. Our current definitions of massive transfusion are outdated. ▫Critical Administration Threshold (CTA): 3 units/hour Alan I. Frankfurt, MD 45

46 Cryoprecipitate 1:1:1:1(?) Alan I. Frankfurt, MD 46

47 ROTEM Radically Alters Transfusion in Combat Casualty Resuscitation Andrew P. Cap 1, Philip C. Spinella 1,3, Nichole K. Ingalls 5, Christopher E. White 1,2, Alejandra G. Mora 1, Heather F. Pidcoke 1, Nicolas Prat 1, Lorne H. Blackbourne 1, Joseph J. DuBose 4 1 United States Army Institute of Surgical Research, Fort Sam Houston, TX , 2 San Antonio Military Medical Center, Fort Sam Houston, TX Washington University in St. Louis, St. Louis, MO 63108, 4 Baltimore CSTARS, R. Adams Cowley Shock Trauma Center / University of Maryland School of Medicine, Baltimore, MD 21201, 5 Nellis Air Force Base, NV *There were 16 and 15 transfused patients respectively in each period that did not receive RBC. x5 MTP RATIO DRIVEN RESUSCITATION ROTEM DRIVEN RESUSCITATION

48 Conclusions 1. DCR utilizing a 1:1:1 ratio driven MTP may underestimate the need for cryoprecipitate and platelets 2. ROTEM driven resuscitation more closely approximated a 1:1:1:1 transfusion ratio. ROTEM Radically Alters Transfusion in Combat Casualty Resuscitation Andrew P. Cap 1, Philip C. Spinella 1,3, Nichole K. Ingalls 5, Christopher E. White 1,2, Alejandra G. Mora 1, Heather F. Pidcoke 1, Nicolas Prat 1, Lorne H. Blackbourne 1, Joseph J. DuBose 4 1 United States Army Institute of Surgical Research, Fort Sam Houston, TX , 2 San Antonio Military Medical Center, Fort Sam Houston, TX Washington University in St. Louis, St. Louis, MO 63108, 4 Baltimore CSTARS, R. Adams Cowley Shock Trauma Center / University of Maryland School of Medicine, Baltimore, MD 21201, 5 Nellis Air Force Base, NV *There were 16 and 15 transfused patients respectively in each period that did not receive RBC.

49 How Much Difference Does Additional Cryoprecipitate and Platelets Make? 2003 Iraq2012 Afghanistan Mortality: >20% ▫No platelets and cryoprecipitate available in theater Mortality: <10% ▫Greater cryoprecipitate and platelets availability.  ISS scores higher in casualties in 2012 than those in Evolving MTP 1:1:1:1 Evolving MTP 1:1:1:1

50 Putting it all together Massive Transfusion Protocol THR Dallas Alan I. Frankfurt, MD 50

51 MTP & Uncontrolled Hemorrhage PYXIS/L&D resuscitationBLOOD BANK resuscitation TXA ▫1-2 grams IV slowly ▫1 gram IVPB over 8 hours riaSTAP ▫2-4 grams IV O negative pRBC (+/- Liquid Plasma) iSTAT ▫Hgb; ABG/VBG; ionized Ca ▫Lactate Round 1 MTP ▫O negative pRBC ▫AB negative FFP ▫(+/- cryoprecipitate) ▫(+/- platelets) Round 2 MTP ▫Type specific pRBC ▫Type specific FFP ▫(+/- cryoprecipitate) ▫( +/- platelets) 51 Alan I. Frankfurt, MD

52 Rethinking the Acceptable Hematocrit and Platelet marginalization during massive hemorrhage 52 Higher Hct increased platelet interaction with the endothelium. Platelet concentrations along the endothelium remains almost x7 that of the average blood concentration. Uijttewall WS et al., Am J Physiol 1993, 264: H1239-H1244

53 Maintain a Hct 35%: Shear stress & platelet margination Alan I. Frankfurt, MD 53 35% 21% Hardy JF et. Can J Anaesthe 2006, 53: S40-S58

54 HCT & Platelet count: Synergistic Effect on Clotting Hct levelPlatelet countPercentage platelet interaction with subendothelium Hct =40%200, / , / , /- 0.8 Hct=20%200, / , / , / Transfusion 1994, Vol. 34, No.6

55 Plasma Alan I. Frankfurt, MD 55

56 Alan I. Frankfurt, MD 56 Thawed shelf life: 5 days Shelf life: 26 days RBC Platelets

57 Plasma deficit vs. Plasma ratio 57 Plasma ratio: pRBC:FFP Vs. Plasma deficit: (Total RBC)-(Total FFP)

58 BLOOD PRODUCT USE IN TRAUMA RESUSCITATION: Plasma deficit versus plasma ratio as predictors of mortality in trauma Andreas R. de Biasis, Lynn G. Stansbury, Richard P. Dutton, Debra M. Stein, Thomas Ml Scalea, and John R. Hess Plasma deficit ▫(Total RBC)-(Total FFP)<2  Mortality was related to plasma deficit, not plasma ratio  0-3 hours post injury  Early plasma availabililty Gold:Red:Gold:Red….. Simultaneous administration of plasma along with pRBC Thawed plasma/Liquid (never frozen) plasma in ED/L&D Lyophilized plasma Unavailable in USA ? Lyophilized fibrinogen 58

59 Future Developments Lyophilized FFP Logistic requirements: ▫Storage  No refrigeration required  Room temperature  Easily transported ▫Quickly reconstituted Rapid volume expansion ▫Rapid 1:1 pRBC/FFP ration obtained Contains all clotting factors Shelf life ▫2 years  Clotting factor ABO considerations ▫No blood typing required French military medicine ▫1994 FDA: compassionate approval for the US military ▫Special forces 59 Alan I. Frankfurt, MD

60 Plasma & the Endothelium (The other 50% of making a strong clot) Alan I. Frankfurt, MD 60

61 Role of the Endothelia Glycocalyx and Resuscitation Fluids Choice Extremely fragile Composition ▫Glycoproteins ▫Proteoglycans Key determinants of membrane permeability in various vascular organ systems mm thickness 1000 cc plasma embedded in the EG. Alan I. Frankfurt, MD 61

62 Alan I. Frankfurt, MD 62

63 Plasma: 1000 different proteins Coagulation factors Immunoglobulin Albumin  Coagulation  Procoagulant  Anticoagulants  Overall health of the endothelium  Resuscitation/Repair of the EG  Hemorrhagic shock 63

64 Early Plasma vs Crystalloid Effects of Resuscitation Fluids on the Integrity of the Endothelial Glycocalyx: 64 Alan I. Frankfurt, MD

65 Review: Transfusion Protocol Version We are here

66 Platelets Alan I. Frankfurt, MD 66

67 Platelets Platelet Storage: “One size does not fit all” Decisions that shaped the policy on PLT storage temperature 67

68 Adapted from: Kuwahara M et al. Arterioscler Thromb Vasc Biol 2002; 22: 329–34. Platelet Aggregation FIRM, BUT REVERSIBLE ADHESION IRREVERSIBLE ADHESION Scanning electron micrograph of discoid, dormant platelets Activated, aggregating platelets illustrating fibrin strands Flowing disc-shaped platelet Rolling ball-shaped platelet Hemisphere-shaped platelet Spreading platelet 22*C 2 hours

69 Platelet Storage: Effects of temperature 22*C ▫5 day life span ▫1-2 hours to “activate” 4*C ▫48 hour life span ▫Immediately “activated”  Refrigeration of platelets abandoned in 1970’s. Logistics vs. Patient requirements 69

70 70 Historical perspective on platelet storage

71 Fibrinogen & Clot strength The 80% Solution Non pregnant state: mg% Pregnant state: (1000) mg% 71

72 Fibrinogen (F1) is the Weak Link in the Clotting System Hemorrhage ▫Rapid depletion of F1 (fibrinogen) Clot formation ▫Fibrin precursor Platelet interaction ▫Activation ▫Binding ▫Aggregation Alan I. Frankfurt, MD 72

73 What is the Optimal Fibrinogen Threshold for Optimal Clot Formation? 73

74 Plasma Fibrinogen levels & Optimal Hemostasis mg/dl ▫Linear increase in clot strength with increasing F1 levels. 625 mg/dl ▫Clot strength equal to whole blood  Pregnancy level > 28 weeks 1000 mg/dl ▫Clot strength equal to x3 whole blood 74 Clot strength vs. Hypercoagulability Nielsin V, Levy J: Fibrinogen and Bleeding: Old Molecule-New Ideas Anesth Analg 2007; 105: 902-3

75 Sources of Fibrinogen: Fresh frozen plasma (FFP) Cryoprecipitate Fibrinogen concentrate ▫riaSTAP  1 grams of riaSTAP/bottle  50cc sterile water ▫US “off label”  Acquired hypofibrinogenemia ▫Europe  Eliminated cryoprecipitate 75 Volume considerations & Preparation time. Allogenic blood products Thawing Typing (ABO if possible) Infection Volume considerations & Preparation time. Allogenic blood products Thawing Typing (ABO if possible) Infection International Journal of Obstetric Anesthesia (2010) 19,

76 Fibrinogen Concentrate RiaSTAP Human donor ▫Pooled plasma product  Lyophilized Viral inactivation Predictable mg content/vial ▫1000 mg/vial No thawing required ▫Pyxis storage ? Thrombogenic potential 76

77 Tranexamic Acid (TXA) Lysine analogue antifibrinolytics Resuscitation in a drawer (pyxis) 77

78 Plasminogen Plasmin Alan I. Frankfurt, MD 78

79 Mode of Action of Lysine Analogue Tranexamic Acid (TXA) Mannucci PM, Levi M. N Engl J Med 2007;356: TXA

80 CRASH-2 Study Alan I. Frankfurt, MD 80

81 Resuscitation in a drawer Factor 1 (fibrinogen) ▫riaSTAP TXA rF7a Combat gauze Calcium Factors: 2, 7, 9, 10 ▫PCC (prothrombin concentrate complex)  Vitamin K dependent factors ▫Factor 8/vWB  Endothelium ▫Lyophilized plasma ▫Platelets  Factor 5  Entegrion  Lyophilized platelets Alan I. Frankfurt, MD 81 Located in the ED/L&D unit pyxis Future

82 Citrate Intoxication & “ionized "Calcium Citrate intoxication ▫90% citrate  FFP & Platelets ▫Calcium & Magnesium Rate of transfusion, not total blood products Measured calcium vs. Ionized calcium ▫Total calcium is normal even when ionized calcium of critically low  Total calcium measures both calcium bound to citrate and free, ionized calcium Alan I. Frankfurt, MD 82

83 Summary Alan I. Frankfurt, MD 83

84 Alan I. Frankfurt, MD 84

85 Damage Control Resuscitation Goals Fibrinogen ▫> mg%  FFP  Cryoprecipitate  risSTAP: fibrinogen concentrate Hct ▫35-40%  Platelet interaction Platelet concentration ▫>100,000 Plasma ▫Plasma deficit < 2  Early plasma administration ▫Endothelial glycocalyx ▫Coagulation factors ▫Anticoagulants pH ▫Base deficit & Lactate Temperature ▫Active warming measures Ionized calcium ▫4 will get you 4  Hypotension unresponsive to volume 85

86 Questions?? Alan I. Frankfurt, M.D. 86


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