Implementation and execution of civilian RDCR programs Minnesota RDCR

Implementation and execution of civilian RDCR programs Minnesota RDCR Donald H Jenkins, MD FACS Associate Professor of Surgery and Director of Trauma Division of Trauma, Critical Care and Emergency General Surgery Saint Marys Hospital, Rochester MN June 2013

Remote Damage Control: Civilian Experience in the Pre-Hospital Setting No Disclosures

Objectives Indications for treatment with blood products for traumatic hemorrhagic shock in the pre-hospital setting Monitoring devices used for coagulopathy and shock Therapeutics utilized in these patients for pre-hospital treatment of casualties Evacuations of long durations compared to rapid ones Methods of implementation to improve rapid incorporation of recently initiated changes in practice

Remote Damage Control Resusc Austere/rural environment patients Modified transfusion strategy Different than those with scene/pre-hospital time < 30 minutes Limited resources available Lack of plasma availability 40% of the population, 60% of the trauma mortality Current treatment options for uncontrolled hemorrhage in this environment are very limited >75% of combat fatalities occur in the field

Hartford Consensus February 2013 Leaders in law enforcement, EMS, military and the American College of Surgeons Recommendations for civilian organizations to improve survival during active shooter scenarios Stress the importance of early and definitive hemorrhage control to maximize survival in the victims.

Hartford Consensus THREAT T - Threat suppression H - Hemorrhage Control RE - Rapid Extraction to safety, A - Assessment by medical providers T - Transport to definitive care

Coagulopathy on Presentation An initial INR 1.5 reliably predicts those military casualties who will require MT. Pts who have a significant injury present with a coagulopathy. Severity of injury and mortality is linearly associated with the degree of the initial coagulopathy. - Schreiber MA, Perkins JP, Kiraly L, Underwood SJ, Wade CE, Holcomb JB. Early Predictors of Massive Transfusion in Combat Casualties. Submitted, J Trauma. - Brohi K, et al. Acute traumatic coagulopathy. J Trauma. 2003.

Background MacLeod JBA et al. Early Coagulopathy Predicts Mortality in Trauma J Trauma 2003 Brohi K et al. Acute Traumatic Coagulopathy J Trauma 2003 By the time of arrival at the ED, 28% (2,994 of 10,790) of trauma patients had a detectable coagulopathy that was associated with poor outcome

Background Mortality was associated with worse Plasma Deficit & The efficacy of the Plasma Repletion occurs within hours de Biasi et al. Early Coagulopathy Predicts Mortality in Trauma Transfusion (Epub, Accepted 2010)

DoD Learned About Thawed Plasma Thawed plasma is FFP that is kept for up to 5 days at 4 C This product should be present upon arrival of the casualty in the ED should be used as a primary resuscitative fluid started in the ED This approach not only addresses the metabolic abnormality of shock, but initiates reversal of the coagulopathy present in the ED. Thawed plasma is used in theater The DoD Level 1 trauma center uses this product Decreases waste by 60-70% - Malone DL, Hess JR, Fingerhut A. Comparison of practices around the globe and suggestion for a massive transfusion protocol. J Trauma, 2006. - Armand R, Hess JR. Treating coagulopathy in trauma patients. Transfus Med Rev 2003.

Early Use of Blood in the Prehospital Setting Mayo Clinic Experience 1993-96 retrospective review Criteria: Hgb<10, shock, hypotension after resuscitation ~2100 helicopter flights, 94 patients received PRBC s (4%, 91% interfacility transfer) 48% trauma patients, 25% GI bleed, 38% AAA Hgb increased from 8.9 to 10.2 after 2 PRBC No transfusion reactions or complications Average 12 u PRBC after admision Age of RBC is < 14 days Air Med J 1998 Zietlow and Berns

Age of Blood and Procoagulant Microparticles Historically, PCMP increases with age of blood 52 trauma patients vs 22 volunteers Higher PCMP with injury; no difference between transfused (n=19)/not transfused 24 hour PCMP decreased with transfusion No decrease if no transfusion Difference widened with increasing transfusion Spinella Crit Care 2009 Jy Transfusion 2011 Rubin Transfusion 2010-12

Catchment Area

Rationale Coagulopathy & the Golden Hour Trauma Induced Coagulopathy (TIC) predicts mortality Plasma and RBC resuscitation should occur early in the hemorrhagic / coagulopathic pt Catchment area / Rural location provides geographic obstacles Regional plasma deficiency

Protocol ED Phase Thawed Plasma Program Developed in Feb 2008 with input from: - Blood Bank Team - Transfusion Medicine - Medical Transport - Trauma, Critical Care and General Surgery Initial 9 months were restricted to in-hospital Emergency Department use Medical and Surgical emergencies - Safety concerns - Utilization of resources

Product immediately available in the Trauma Resuscitation Area: - 4 units thawed plasma (A+) - 4 units PRBCs (0 negative) Order of transfusion for trauma patients was: 2 units PRBC 2 units thawed Plasma 2 units PRBC 2 units thawed Plasma

Protocol Helicopter Phase Indications for PRBC and Plasma administration in adult trauma patients prbc + Plasma 1. Hypotension (single reading of systolic blood pressure < 90mmHg) 2. Tachycardia (single reading of heart rate 120) 3. Penetrating mechanism 4. Point of care lactate 5.0 mg/dl 5. Point of care INR 1.5 Plasma Alone 1. Point of care INR 1.5 2. Stable Hemodynamics

Waste Prevention Division of Transfusion Medicine monitors usage - Thawed plasma is removed from the satellite blood refrigerator on Day #3 and sent to the Operating Theater for immediate use.

Mayo Helicopter Transfusion Criteria

5 for hemorrhage RESULTS 10 TRAUMA PATIENTS TRANSFUSED IN FLIGHT 2/2009 9/2010 3 required massive transfusion (> 10 units/24 hours) 5 pts transfused for history of trauma and coumadin use All 4 deaths were in this group All pts entered into protocol required ongoing blood product transfusion after arrival to the hospital.

Trauma Patients (n=10) Age (years) Male ISS LOS (days) Mortality 71.5 [30-75.3] 8/10 25.5 [16.8-29.3] 4.5 [1.8-24.8] 4/10

Admission Laboratory Values Coumadin 5/10 (50%) Lactate 2.8 [1.7-5.7] Base -4.1 [-12.5- -0.5] PLT 149 [114-180] PTT 30 [28-42] HgB 10.8 [10.1-13.5] Post-Flight INR 1.6 [1.3-2.8] Pre-Flight INR 2.7 [1.6 4.0]

Feasibility Excellent utilization No discarded units of plasma to date No transfusion reactions documented to date; use of product parallels massive transfusion in the standard setting

Protocol Evolution During the study period, total of 771 flights Only two pts received all 4 units of PRBC during transport Product Order and Ratio 2009: 2 PRBC, 2 Plasma, 2 PRBC 2010: 2 Plasma, 2 PRBC, 2 PRBC 2011: 3 Plasma, 3 PRBC

Hemostatic Resuscitation in Our Trauma Center Pre-hospital plasma and POC testing INR/Lactate pre-hospital Early Diagnosis in ED StO2/i-Stat 1:1 ratio (thawed plasma to RBC) Plasma-first transfusion sequence ED use of PCC? Frequent TEG and early platelet use Minimal crystalloid Repeated doses of PCC and/or transfusion in OR and ICU as required by TEG Young red cells (<14 days)

Ratios / Plasma Balance PTP (n=9) Control (n=50) p En Route P:RBC 1.3 : 1.0 N/A <0.001 30 min P:RBC 1.3 : 1.0 0.14 : 1.0 <0.001 6 hr P:RBC 1.0 : 1.0 0.42 : 1.0 <0.001 24 hr P:RBC 1.0 : 1.0 0.45 : 1.0 <0.001 En Route Plasma Deficit - 0.4-1.0 0.32 30 min Plasma Deficit - 1.2-2.0 0.37 6 hr Plasma Deficit - 1.7-5.3 0.06 24 hr Plasma Deficit - 1.0-5.7 0.04

Time & the Geographic Plasma Deficit PTP (n=9) Control (n=50) p Facility Transfer 100% 54% 0.002 Transport à Trauma Ctr (min) 40 39 0.78 Injury à First Plasma (min) 194 231 0.58 Trauma Ctr arrivalà Plasma (min) - 34 97 0.013

Inaba K et al. Arch Surg 2010 Group A Plasma Transfusion Introduction ABO-identical preferred Universal plasma donor Group AB Lacks anti-a/anti-b Pan-ABO compatible Rarest blood group

Isaak EJ et al. Immunohematology 2011 Josephson CD et al. Transfus Apher Sci 2010 Group A Plasma Transfusion Group AB supply Recent safety data ABO incompatible platelets 1 2 plasma units 1 in 9000 hemolysis Group O Immunosuppression

Group A Plasma Transfusion Results 10,206 patients over study period Trauma patient July 2008 June 2012 1 unit emergency release plasma (group A plasma) 258 emergency release plasma (2.5%) 4 died prior to blood grouping

Group A Plasma Transfusion Results 254 patients 35 ABO Incompatible (14%) 25 group B 10 group AB 219 ABO Compatible (86%) 116 group A 103 group O

Group A Plasma Transfusion Results Feature ABO Incompatible n = 35 ABO compatible n = 219 P Age (years) 56 (39-79) 59 (32-79) 0.944 Male sex 63% 63% 0.973 ISS 25 (16-37) 22 (12-30) 0.199 TRISS 0.86 (0.26-0.97) 0.93 (0.34-0.97) 0.880 Scene transfer 34% 38% 0.710 Time from injury to trauma bay admission (mins) 145 (54-185) 172 (92-230) 0.214 Time in trauma bay (mins) 24 (20-35) 26.5 (20-36) 0.883 Time at referring hospital 119 (96-144) 121 (70-172) 0.920

Group A Plasma Transfusion Results ABO Incompatible n = 35 ABO compatible N = 219 P Ventilator days 6 (2-12) 3 (2-8) 0.070 ICU LOS (days) 4 (1-11) 3 (1-7) 0.155 Hospital LOS (days) 9 (3-24) 7 (3-17) 0.146 Complications 43% 35% 0.449 ALI 3.7% 2.5% 0.542 Possible TRALI 2.9% 3.0% 0.362 ARDS 2.9% 1.8% 0.527 Pneumonia 17% 9% 0.144 DVT 2.9% 4.1% 1.00 PE 5.8% 7.3% 1.00 Acute renal failure 0% 1.8% 0.420 Mortality Sepsis 0% 0.5% 0.689 20% 22% 0.798

Group A Plasma Transfusion Results ABO Incompatible n = 35 ABO compatible N = 219 P Ventilator days 6 (2-12) 3 (2-8) 0.070 ICU LOS (days) 4 (1-11) 3 (1-7) 0.155 Hospital LOS (days) 9 (3-24) 7 (3-17) 0.146 Complications 43% 35% 0.449 ALI 3.7% 2.5% 0.542 Possible TRALI 2.9% 3.0% 0.362 ARDS 2.9% 1.8% 0.527 Pneumonia 17% 9% 0.144 DVT 2.9% 4.1% 1.00 PE 5.8% 7.3% 1.00 Acute renal failure 0% 1.8% 0.420 Mortality Sepsis 0% 0.5% 0.689 20% 22% 0.798

Group A Plasma Transfusion Results ABO Incompatible n = 35 ABO compatible N = 219 P Ventilator days 6 (2-12) 3 (2-8) 0.070 ICU LOS (days) 4 (1-11) 3 (1-7) 0.155 Hospital LOS (days) 9 (3-24) 7 (3-17) 0.146 Complications 43% 35% 0.449 ALI 3.7% 2.5% 0.542 Possible TRALI 2.9% 3.0% 0.362 ARDS 2.9% 1.8% 0.527 Pneumonia 17% 9% 0.144 DVT 2.9% 4.1% 1.00 PE 5.8% 7.3% 1.00 Acute renal failure 0% 1.8% 0.420 Mortality Sepsis 0% 0.5% 0.689 20% 22% 0.798

Group A Plasma Transfusion Results Product ABO Incompatible N = 35 ABO compatible N = 219 P Emergency release plasma (units) 2 (1-4) 2 (1-4) 0.345 Total Incompatible Units 3 (2-4) 0 (0-0) <0.001 Total compatible units @ 24 hours Total plasma @ 24 hours (units) 2 (0-6) 3 (2-6) 0.439 6 (3-10) 4 (2-7) 0.444 Total RBC @ 24 hours (units) 5 (0-12) 4 (0-8) 0.472 Plasma:RBC @ 24 hours 1.3:1 1.1:1 0.155 Plasma deficit @ 24 hours 2 (0-3) 1 ( - 1-3) 0.195 Total Platelet units @ 24 hours 0 (0-2) 0 (0-1) 0.801

Group A Plasma Transfusion Results Product ABO Incompatible N = 35 ABO compatible N = 219 P Emergency release plasma (units) 2 (1-4) 2 (1-4) 0.345 Total Incompatible Units 3 (2-4) 0 (0-0) <0.001 Total compatible units @ 24 hours Total plasma @ 24 hours (units) 2 (0-6) 3 (2-6) 0.439 6 (3-10) 4 (2-7) 0.444 Total RBC @ 24 hours (units) 5 (0-12) 4 (0-8) 0.472 Plasma:RBC @ 24 hours 1.3:1 1.1:1 0.155 Plasma deficit @ 24 hours 2 (0-3) 1 ( - 1-3) 0.195 Total Platelet units @ 24 hours 0 (0-2) 0 (0-1) 0.801

Group A Plasma Transfusion Results Product ABO Incompatible N = 35 ABO compatible N = 219 P Emergency release plasma (units) 2 (1-4) 2 (1-4) 0.345 Total Incompatible Units 3 (2-4) 0 (0-0) <0.001 Total compatible units @ 24 hours Total plasma @ 24 hours (units) 2 (0-6) 3 (2-6) 0.439 6 (3-10) 4 (2-7) 0.444 Total RBC @ 24 hours (units) 5 (0-12) 4 (0-8) 0.472 Plasma:RBC @ 24 hours 1.3:1 1.1:1 0.155 Plasma deficit @ 24 hours 2 (0-3) 1 ( - 1-3) 0.195 Total Platelet units @ 24 hours 0 (0-2) 0 (0-1) 0.801

Group A Plasma Transfusion Discussion Emergency plasma use is increasing Limited access New universal donor resulted in 97.6% reduction in AB plasma use

Group A Plasma Transfusion Discussion Group A plasma has equivalent outcomes to group AB Incompatible transfusions occurred No hemolytic reactions Similar mortality Similar immunogenic complications Limitations Small comparison group Type II error potential

CRASH-2 Study Lancet, Online Article, 2010 Prospective, randomized controlled trial 20,211 patients TXA significantly reduced all cause mortality from 16.0% to 14.5% TXA significantly reduced death due to bleeding from 5.7% to 4.9% 43

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StO2

Beilman Study Over a 15-month period, seven Level I trauma centers in the USA enrolled 383 patients, 50 of whom developed MODS StO2 below 75% indicates serious hypoperfusion in trauma patients 78% of patients who developed MODS, and 91% of patients who died, had StO2 below 75% in the first hour Trauma patients who maintained StO2 above 75% within the first hour had an 88% chance of MODS-free survival J Trauma 2006

Can early StO2 predict the need of blood product requirement in trauma population? Total 632 level 1 trauma 325 patients with recorded StO2

Scene Assessment Variable StO2< 65 n=23 StO2>65 n=302 p Systolic blood pressure, (SD) Heart rate, (SD) NS NS

Emergency Department Assessment Variable StO2< 65 n=23 StO2>65 n=302 Systolic blood pressure, (SD) 0.23 Heart rate, (SD) 0.39 Respiratory rate, (SD) 0.06 O2 saturation, (SD) 0.2 Temperature, (SD) 36.1 (1.2) 36.6 (0.7) Trauma score, (SD) 9 (2) 10 (2) Glasgow coma score, (SD) 7.7 (6) 10 (6) p

Laboratory Results and FAST Variable StO2< 65 n=23 StO2>65 n=302 p Hemoglobin, (SD) Hematocrit, (SD) ph, (SD) Base deficit, (SD) Lactate, (SD) 3.9 (3.2) 2.4 (2.1) FAST done Positive FAST NS NS NS NS NS NS

Outcomes Variable StO2< 65 N=23 StO2>65 N=302 p ICU days, (SD) Hospital length of stay, (SD) Mortality Surgical interven.on 18 (78%) 152 (50%) Morbidity 11 (48%) 68 (23%) NS NS NS

Multivariate analysis Variable StO2 < 65% 0.01 Systolic BP 0.11 Heart rate 0.97 O2 satura.on 0.91 Lactate level 0.25 Age 0.32 ISS 0.33 GCS 0.74 Posi.ve FAST 0.19 p

Current Status All 3 Mayo helicopter bases carrying 3 PRBC and 3 thawed plasma All 3 use same transfusion triggers All 3 use i-stat INR and ABG cartridges All 3 carry TXA; uses similar triggers but has some limitations for use Just added StO2 as a trigger Limited waste at all 3 sites No crystalloid for those with hemorrhage Tourniquets and Combat Gauze on all 3 ships

The Future Freeze dried plasma? Whole blood? Platelets? Prothrombin complex concentrates?

Why Freeze Dried Plasma? Remote Damage Control Resuscitation!

Implementation of Change Consensus Review of the literature and our own data Practicality and safety are first order of business with best interest of patient in mind Continuous monitoring of program Education of all health care providers Willingness of blood bank and transfusion medicine to consider novel use of products

Overall System Results Current era (2011) compared to the era before pre-hospital plasma Referrals up (838 vs 998*) ISS up (9 vs 12*) Mortality same (2.5% vs 2.2%) Observed decline open abdomen (under study) Observed decline in massive tx (under study) Arrival TEG improved? (under study)

Summary Trauma patients die from shock Our job is to limit preventable trauma death First, identify the patient in shock Pre-hospital resuscitation with plasma can prevent the trauma induced coagulopathy and limit the risk of death due to hemorrhage Making dried plasma available in the rural and pre-hospital/austere environment will save lives

Thank You!

Questions?