1. Missouri EMS Central Region November 2011 Webinar Contemporary Fluid Resuscitation Jeffrey Coughenour, MD, FACS Assistant Professor of Surgery Medical Director, Missouri EMS Central Region

2. Purpose Monthly educational opportunity for providers within the Central Region Focus – Performance improvement, actual case review – Literature review – Discuss practice management guidelines

4. Objectives Introduce contemporary trauma resuscitation and review the supporting evidence – Damage-control or hemostatic resuscitation – Massive transfusion – Hypertonic saline – Other adjuncts for coagulopathy

6. Origins Walter B. Cannon Fight or Flight Traumatic Shock, 1923 CNS-mediated “toxic factor” released from tissue “…if the pressure is raised before the surgeon is ready to check the bleeding that may take place, blood that is sorely needed may be lost”

7. Shock Combination of classic shock states – Loss of circulating blood (hemorrhagic) – Myocardial depression (cardiogenic) – Hypoperfusion or reperfusion injury (neurogenic) End result—decreased oxygen delivery and cellular dysfunction

8. Shock Compensated shock – Increase in HR, vasoconstriction of non-essential ischemic-tolerant vascular beds Decompensated shock – Lack of adequate oxygen delivery builds up “oxygen debt”, leads to cellular dysfunction and damage, reperfusion injury, reversible

9. Shock

10. Dogma LR or NS then PRBC’s – LR Diarrhea fluid from 1880, acidotic, no clotting factors, 200 mL intravascular at 60 min, proinflammatory – PRBCs Each unit increases MOF, old blood = high K+, acidotic, no clotting factors, immunosuppressive Standard resuscitation approach was to escalate use of fluids that may worsen abnormal physiology – 2L LR (3:1), then PRBC (10 units), then FFP (2 units)

14. Pre-Hospital IV Fluid Administration is Associated with Decreased Survival in Severely Injured Trauma Patients Abstract, EAST 2009, Haut ER et al NTDB analysis, mortality as primary outcome analysis Subgroup analysis: Mechanism, ISS, hypotension, coma, need for immediate surgery 776,734 patient data sets evaluated – Unadjusted mortality higher 4.8 vs. 4.5% (p<0.001) – Odds Ratio of death for IV fluid group—1.3 – Subset analysis consistent in all groups – Association greatest in penetrating mechanism, hypotension, need for immediate surgery

15. Damage Control or Hemostatic Resuscitation

16. Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report Martin, Bickell, Pepe, Burch, Mattox J Trauma 1992 Sep;33(3):354-61; discussion 361-2 Randomization of immediate vs. delayed fluid resuscitation is penetrating truncal injury with hypotension (< 90 mmHg) Immediate n=96, 56% survival to discharge Delayed n=81, 69% survival to discharge Survival advantage not statistically significant All other endpoints, little difference

17. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries Bickell, Wall, Pepe, Martin, Allen, Mattox N Engl J Med 1994 Oct 27;331(17):1105-9 598 adults randomized to immediate or delayed resuscitation Immediate group – 62% survival, 30% one or more complications Delayed group – 70% survival, 23% complications Survival p-value=0.04 Complications: ARDS, sepsis, ARF, coagulopathy, wound infection, pneumonia

18. Fundamental Change Delay in hemorrhage control—early preventable deaths Large-volume crystalloid followed by transfusion worsens reperfusion injury and systemic inflammation—late preventable deaths New methods of resuscitation and monitoring required to prevent late trauma deaths

23. Select Population About 10% of injured will be hypotensive Of those, 3-5% due to blood loss Early identification of – Abnormal physiology – Injury parameters Pre-determined resuscitation strategy

24. Pattern Recognition Exam findings – Decreased mental status from injury or shock – Suspected TBI – Clinical coagulopathy Laboratory values – INR > 1.5 – Base deficit > 6 – Hemoglobin < 11 – Hypothermia (<96) or hypotension (SBP <90)

25. Pattern Recognition Trunk, axillary, groin, or neck wounds not controlled by local wound care – Direct pressure – Tourniquet – Hemostatic dressings Proximal amputation or mangled extremity Hemoperitoneum with shock Massive hemothorax – >2000 mL initially or >200 mL per hour for 4 hours

26. Hemostatic Resuscitation Crystalloid to maintain radial pulse, alertness PRBC:FFP 3:2 PRBC:Platelets 5:1 Adjuncts for coagulopathy With cessation of hemorrhage and normalization of physiology, minimal crystalloid

27. Hypertonic Saline

28. Hypothesized benefits – Intravascular volume expansion – Immunomodulatory – Improved microcirculatory flow – Inotrope via myocardial sodium channels Optimal formula ? – 3%, 7.5%, 7.5% with dextran

29. Hypertonic Resuscitation of Hypovolemic Shock after Blunt Trauma: A Randomized Controlled Trial Bulger EM, Jurkovich GJ, Nathens AB Arch Surg 2008 Feb;43(2):139-48 250 mL of 7.5% hypertonic saline and 6% dextran (HSD) vs. LR 209 patients enrolled, stopped (futility) after second data analysis No significant difference in ARDS-free survival Benefit in subset requiring >10 unit transfusion in first 24 hours

30. Prehospital resuscitation with hypertonic saline- dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients Rhind SD, Baker AJ, Morrison LJ, et al J Neuroinflamm 2010 Jan 18;7:5 Impact of prehospital resuscitation on selected cellular and soluble inflammatory/coagulation markers Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules HSD attenuated the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators

31. Blood and Blood Component Therapy

32. Massive Transfusion MOF lower, 9 vs 20%, p < 0.01 30 day survival higher 57 vs 38%, p < 0.01 Benefit = earlier product administration JTrauma 2009

35. More than 20 papers involving > 2,000 patients In severely injured patients, early product administration resulted in less product use and increased survival

36. Fresh Frozen Plasma Is Independently Associated With a Higher Risk of Multiple Organ Failure and ARDS The Inflammation and the Host Response to Injury Investigators J Trauma 2009 Aug 67(2):221-230 Investigate effect of plasma rich components of resuscitation after blunt trauma N= 1,175 (65% FFP, 41% platelets, 28% cryo) With each unit of FFP, odds ratio 2.1 and 2.5 for MOF and ARDS

37. An FFP:PRBC Transfusion Ratio >/=1:1.5 is Associated With a Lower Risk of Mortality after Massive Transfusion The Inflammation and the Host Response to Injury Investigators J Trauma 2008 Nov;65(5):986-93 In civilian blunt trauma patients requiring ≥ 8 units PRBCs in the first 12 hours… – 52% mortality reduction – No effect on MOF or nosocomial infections – Two-fold increase in ARDS

39. Lyophilized Plasma for Resuscitation in a Swine Model of Severe Injury Nicholas Spoerke, MD; Karen Zink, MD; S. David Cho, MD; Jerome Differding, MPH; Patrick Muller, BS; Ayhan Karahan, MD; Jill Sondeen, PhD; John B. Holcomb, MD; Martin Schreiber, MD Arch Surg 2009;144(9):829-834 LP clotting factor activity decreased average 14% Survival, HR, blood loss, lactate, coagulation profiles similar between PRBC:FFP and PRBC:LP groups Decreased IL-6 production with LP However, not likely available for several years…

41. Adjuncts Recombinant Factor VIIa – Creates thrombin burst, safe, pH > 7.2 Prothrombin complex concentrates – Hemophilia, emergency reversal of Coumadin Tranexamic acid – Stops pathologic clot-breakdown (fibrinolysis) after massive hemorrhage

42. Summary Points Surgical hemorrhage control is paramount! Limitation of the amount of crystalloid improves outcomes Early blood products in pre-determined amounts are effective rFVIIa, PCC, and tranexamic acid are likely useful adjuncts to hemostatic resuscitation

43. Summary Points www.pubmed.com Search hypotensive, hemostatic, or damage- control resuscitation

44. December 2011 Webinar The Surgical Airway

45. Questions ? www.muhealth.org/acutecaresurgery