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Damage Control Resuscitation John B. Holcomb, MD, FACS Professor and Vice Chair of Surgery University of Texas Health Science Center, Houston, TX 1 Nothing to Disclose 2 Texas Trauma Institute Houston, TX 3 Memorial Hermann-TMC and UT Health Trauma Volume - 2012 Update slide 4 May 2, 2013 • In 2010, there were 5.1 million deaths from injuries — 10% of all deaths — and the total number of deaths from injuries was greater than the number from infection with HIV, tuberculosis, and malaria combined (3.8 million). • Overall, the number of deaths from injuries increased by 24% between 1990 and 2010. 5 Years of Potential Life Lost (YPLL) Before Age 65 Cause of Death Percent All Causes Unintentional Injury Suicide Homicide Malignant Neoplasms Heart Disease Perinatal Period Congenital Anomalies Cerebrovascular HIV Liver Disease All Others YPLL 948,426 199,903 52,265 48,190 137,221 107,009 75,496 43,615 21,817 21,508 21,352 220,050 100.0% 21.1% 5.5% 5.1% 14.5% 11.3% 8.0% 4.6% 2.3% 2.3% 2.3% 23.2% 31.7% The National Center for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System. US Department of Health and Human Services, CDC; 2008. Available at: http://www.cdc.gov/ncipc/wisqars/. Accessed May 22, 2009. 6 UTHSC-Houston 1999-2008 Trauma admissions = 36,028 and 2394 deaths = 6.6% Early deaths (≤ 24 hrs) = 1398 or 58% 30 25 % 20 15 72 hrs = 72% 24 hrs = 58% 6 days = 92% 30 days = 97% 10 5 0 Deaths from day 31-171 = 68/2394 = 3% 7 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 – Must have thawed/liquid plasma in the ED to really do this well • Time is critical 9 How to Resuscitate? • Its not just raise the BP – Not just the hole in the blood vessel that needs rapid suture • Why do we give RBCs first? – Red stuff • Reverse the systemic and iatrogenic endothelial injury – Reverse permeability – Prevent edema – Repair the endothelium • Dampen the systemic inflammatory response • Prevent and Reverse coagulopathy • Time is important 10 J Trauma, 2007. • Rapid progress in trauma care occurs during a war. • Damage control resuscitation addresses diagnosis and treatment of the entire lethal triad immediately upon admission. 11 DCR components • • • • • • • Stop bleeding Hypotensive resuscitation Minimize crystalloid Use thawed plasma to resuscitate patients Increased platelet use Reverse hypothermia and acidosis Hemostatic adjuncts 12 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 14 17 yr, GSW Liver, 60/30, BD-17 • • • • 2010 11 RBC 10 FFP 2 platelet 3 liters crystalloid • 3 ops • Home in 8 days Rt pulmonary lower lobe wedge, Rt hepatic lobectomy, Rt nephrectomy 14 RBC 14 FFP 2 platelets 2 cryo 2 liters of crystalloid 2014 Post Operative Damage Control Laparotomy and Thoracotomy 5 days post op Home day 10 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 •Armand & Hess, Transfusion Med. Rev., 2003 WWB: 500 mL Warm Hct: 38-50% Plt: 150-400K Coag: 100% 1000 mg Fibrinogen Which one to use, start, how much, stop ?? 21 J Trauma, 2007 70 65% Mortality 60 2003-2004, n = 252 P < 0.05 50 40 30 34% 16231 20 53 19% 162 10 0 (Low) 1:8 (Medium) 1:2.5 (High) 1:1.4 23 Ann Surg 2008 • Multicenter (16) Retrospective Massive Transfusion Study • 12 months data collection • ≈ 30,000 admissions and ≈11,650 transfused – 466 MT’s 24 30 day Kaplan-Meier 25 JACS 2010 12 hrs 24 hrs 26 Ann of Surg, 2011 2004-2008 vs 2008-2010 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. 28 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) 29 How do you make early blood products happen? • Work with the Blood bank and Donor Center • O- RBCs—in the ED • AB or A plasma—in the ED –Thawed or Liquid plasma • Platelets—in the ED? • Prehospital? 30 JAMA Surg, 2013 • Implementation of a ED-TP protocol: – Decreased time to first plasma transfusion (89 vs 43 minutes, p.= .001). • The TP-ED protocol was associated with a reduction in 24-hour transfusion of RBCs (p=.04), plasma (p=.04), and platelets (p=.001). • Logistic regression identified TP-ED as an independent predictor of decreased 30-day mortality (p=.04). 31 JAMA Surg 2013 • 3.6% 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, – range, 1.7-5.4 hours 32 Transfused = 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 33 PROMMTT plasma:RBC Hem death at 2.6 hrs 34 PROMMTT platelets:RBCs Hem death at 2.6 hrs 35 PROMMTT • Data suggest that earlier and higher ratios of plasma and platelets were associated with decreased in-hospital mortality in the first 6 hours. – 1:1:1 is superior to 1:1:2 36 J Trauma 2013 The incremental amount of crystalloid rather than the amount of blood products transfused during the first day of care seems to be the modifiable risk factor for lung injury. TRALI (0) vs CRALI (505)? 38 Lots of work over a long time All the retrospective studies Whole Blood vs Components Study Frozen Blood vs Stored Blood All funded by DoD 39 J Trauma, 2011 J Trauma 2011 J Trauma 2012 41 R-TEG Graphical Display in the ED • We no longer send PT / PTT / INR, fibrinogen and platelet counts Ann Surg 2012 UT Health Science Center and Memorial Hermann Hospital Houston, TX Summary • Considering the speed, charges, and global functional information obtained, TEG is superior to CCTs. – acute care surgery group, emergency medicine, orthopaedics, anesthesia, neurosurgery, pediatric surgery How we use TEG 48 • • 2005-2011, 1412 (4.7%) patients sustained blunt liver injury. AAST Grade IV and V injuries accounted for 244 (17%) patients, of which 206 patients survived to leave the ED. – • The DCR cohort had an increase in successful non-operative management – • Pre DCR vs DCR 54 to 74%, p<0.01 The DCR treatment cohort resulted in improved survival – 73% to 94% (p<0.01). 49 Survival of Grade 4 and 5 Liver Injury over 7 years n = 206 Survival 100 Percentage of patients 90 80 Survival 70 60 2005 2006 2007 2008 Years 2009 2010 2011 50 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 51 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. 52 Fold decrease in permeability above control Pulmonary Endothelial Cell Permeability 10 Day 0 Day 5 Day 10 LR LP 8 6 4 2 0 5% 10 0% 30 % 5% 5% 10 0% 30 % 5% 10 0% 30 % -4 10 0% 30 % 5% 10 0% 30 % -2 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 J Trauma, 2010 Anes & Analg, 2011 The glycocalyx is a ubiquitous barrier that protects the underlying endothelium and prevents injurious neutrophilendothelial interaction. A B C D A = baseline B= shock C = LR resus C = Plasma resus 54 Shock 2012 NS Hextend FFP 55 Stem Cells and Dev 2011 56 57 Prehospital and Hospital • No distinction • Should be a seemless continuum • What works in the hospital should be used prehospital 58 Ann Surg 2013 59 RBC and FFP on Helicopters • • • • • 19 months 4 helicopters 2 units O- and 2 units thawed AB plasma Indications for transfusion same as in the ED 150 trauma patients – 90% continued receiving products in the ED – Improved early survival 60 Back to the Future Lyophilized Plasma Resuscitation 61 Dried Plasma in the IDF 62 Shock, 2013 63 Dried Plasma Product Carried by US Special Operations Forces 64 Different ProCoagulants Many US Companies Working on dried plasma 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 66 Concept • Not rigidly ratio driven • Not rigidly TEG (or ROTEM) driven • Incorporates the elements of time and logistics and personnel specific to our site • Plasma is our primary resuscitation fluid 67 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 68