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Transfusion Practices with Combat Wounded

Transfusion Practices with Combat Wounded. Francis (Frank) M. Chiricosta, LTC, MC Transfusion Medicine Consultant, US Army. Overview. Massive Transfusion / Coagulopathy Resuscitation change in practices Traditional Guidelines / Practices Use of plasma Use of Fresh Whole Blood Factor VIIa

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Transfusion Practices with Combat Wounded

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  1. Transfusion Practices with Combat Wounded Francis (Frank) M. Chiricosta, LTC, MC Transfusion Medicine Consultant, US Army www.milblood.mil

  2. Overview • Massive Transfusion / Coagulopathy • Resuscitation change in practices • Traditional Guidelines / Practices • Use of plasma • Use of Fresh Whole Blood • Factor VIIa • Age of blood www.milblood.mil

  3. Hemorrhagic Mortality • While bleeding is the #2 cause of mortality, hemorrhage is the #1 reversible cause for mortality • Bleeding to death is an acute problem • Almost all mortality from hemorrhage occurs within 1st 24 hours • Early control of hemorrhage can save lives Data adapted from: Acosta, et al. J Am Coll Surg 1998 & Sauaia, et al. J Trauma 1995 www.milblood.mil Slide courtesy JG Perkins

  4. Massive transfusion • One body volume in 24 hours • “Dilutional” coagulopathy • depleted coagulation factors • thrombocytopenia • hypoperfusion • confounding conditions: DIC, sepsis www.milblood.mil

  5. N=450 combat casualties in the Vietnam War on Admission Hematocrit % 20 40 Heart Rate (BPM) 70 90 110 130 150 Lactate mg/100 mL 20 40 60 80 100 Base Deficit mEq/L 0 2 4 6 8 10 Pathophysiology of Trauma • With decreased blood pressure • Base deficit increased • Lactate Increased • Hematocrit Modestly Decreased • Heart Rate Increased Adapted from: Collins JA, Simmons RL, James PM, Bredenberg CE, Anderson RW, Heisterkamp CA 3rd.The acid-base status of seriously wounded combat casualties. I. Before treatment. Ann Surg. 1970 Apr;171(4):595-608. Slide courtesy JG Perkins

  6. Pathophysiology of Trauma Acidosis Coagulopathy Hypothermia

  7. Traditional resucitation • Replace lost volume first with crystalloid • May be able to restore normal BP • Blood transfusion comes later • Potential complications of aggressive fluid resuscitation • “Pop the clot” • Hemodilution • Coagulopathy • Hypothermia • Acidosis www.milblood.mil

  8. Damage Control Resucitation • Do not replace volume quickly • Hypovolemia / hypotension is tolerated • Stop bleeding • Correct abnormal physiology later • “... inaccessible or uncontrolled sources of blood loss should not be treated with intravenous fluids until the time of surgical control.” --Cannon WB, FaserJ, CollewEM: The preventive treatment of wound shock. JAMA, 47:618, 1918 1918! Not a totally new idea www.milblood.mil

  9. Coagulopathy of Trauma • Hemodilution due to resucitation… and • Coagulopathy that is due to the trauma itself • Evidence that coagulopathy starts before fluid resuscitation; not a dilutional coagulopathy • Molecular mechanism: thrombomodulin, protein C (Brohi, K) www.milblood.mil

  10. Massive Transfusion,Transfusion considerations • assessment: clinical and lab together • microvascular bleeding • PT/PTT > 1.5 nl, plt < 50 – 100 • Warm patient • one 6-pk platelets roughly same coag. factors as U FFP • Plt, CRYO, FFP short/difficult supply • Fresh whole blood www.milblood.mil

  11. Massive Transfusion,Problematic transfusion management • Transfused plasma is foreign to recipient; has anti-A, -B; A substance, B substance • ABO incompatible plasma (e.g. type O rbc/WB/Plt to type A patient) may be associated with adverse outcome (Blumberg, N) www.milblood.mil

  12. Massive Transfusion,complications • Citrate toxicity • Hypocalcemia, prolonged QT • With normal liver, not generally a problem • Rapid infusion centrally can be a problem • Alkalosis with metabolism • Hyperkalemia? • Usually the opposite: with metabolic derangement, K+ goes low • Theoretic problem in renal failure www.milblood.mil

  13. Massive Transfusion,complications • Hypothermia (use of blood warmer) • PT/PTT elevation • Platelet dysfunction • Dilutional coagulopathy • Old blood is bad blood? • Transfusion reactions • More error prone • Less likely to recognize www.milblood.mil

  14. Packed Red Blood Cellspurpose of the transfusion • To increase oxygen carrying capacity in an anemic patient when it is needed • Need is based on clinical assessment of risk of complications of low oxygen delivery (e.g.. when cardiac oxygen demand increases to increase cardiac output) www.milblood.mil

  15. Traditional Guidelines www.milblood.mil

  16. Existing Guidelines • Red cell transfusion • Purpose: oxygen carrying • loss of 30%+ of blood volume • normovolemic, P>100, SBP<100, ssx • Diluent: normal saline only • Assessment: clinical; H/H may not be valid • Golden Hour www.milblood.mil

  17. Red Cell Indicationsclinical studies • Hébert, et al. 1999 • randomized, controlled clinical trial, 838 critically ill patients • liberal group: Hb tx. trigger 10g/dl • restrictive group: trigger 7 g/dl • findings: • overall 30-day mortality similar (p=0.11) • lower rates for restrictive group for less acutely ill and age<55 (p=0.02, 0.03) • in-hospital mortality rate lower in restrictive group (p=0.05) www.milblood.mil

  18. Red Cell Indicationsclinical studies • Hébert, et al. 1999 • findings: • liberal group had significantly higher rates for: • MI (p=0.02) • pulmonary edema (p<0.01) • no significant difference in other complications • trend toward lower 30-day mortality in restrictive group • decreased blood exposure in restrictive group www.milblood.mil

  19. Red Cell Indicationsclinical studies • Carson, 1998 • almost 9000 patients 60 years and older getting hip fracture repair • at pre-transfusion Hb (“trigger”) of 8 to 10 g/dl, no difference in 30- and 90-day mortality between transfused and not transfused • Weiskopf, 1998 • experiment in isovolemic hemodilution in 23 healthy adults • Hb as low as 5g/dl tolerated at rest www.milblood.mil

  20. Treating Bleeding Related to Coagulation AbnormalitiesPlatelets, FFP, and CRYO • General rule: If bleeding greater than expected and is of a microvascular nature and lab values meet threshold (or not available in time or dysfunction of hemostasis is known or suspected) www.milblood.mil

  21. Microvascular Bleeding • surgical: wetness/oozing from all or most exposed tissue, no visible vessel to mechanically stop • non-surgical: • ecchymosis at sites other than surgical wound • oozing around catheters; from mucosal surfaces www.milblood.mil

  22. PlateletsIndications, Guidelines and Practice Parameters • American Society of Anesthesiology • Prophylactic transfusion is rarely indicated if thrombocytopenia is due to increased destruction • With surgery, • usually not indicated >100,000 • usually indicated <50,000 • between 50 and 100,000: base on risk of bleeding • With microvascular bleeding, • same guidelines as for surgery • known platelet dysfunction • Procedures associated with insignificant blood loss may be done <50,000 www.milblood.mil

  23. Fresh Frozen PlasmaIndications, Guidelines and Practice Parameters • American Society of Anesthesiology, 1996 • urgent reversal of warfarin effect • correction of known factor deficiency • for correction of microvascular bleeding in the presence of elevated (>1.5 x nl.) PT or PTT • for correction of microvascular bleeding in a patient who has received >1 blood volume www.milblood.mil

  24. Fresh Frozen PlasmaIndications, Guidelines and Practice Parameters • College of American Pathologists, 1994 • with active bleeding or procedure and • PT* 1.5 x midpoint of normal (18s) or • PTT* 1.5 x top of normal (51s) • in massive transfusion with microvascular bleeding and coagulation abnormality *fibrinogen must be normal, >100mg/dl; patient not on heparin www.milblood.mil

  25. Fresh Frozen PlasmaInappropriate Use • Volume expander, Source of albumin, When heparin is cause of lab abnormality, When a specific therapy is available (VIII, IX, ATIII, Vitamin K, DDAVP) • On a routine schedule with red cell transfusion (prophylactically in massive transfusion) British JH 2004 www.milblood.mil

  26. Evidence against Routine Schedule of Plamsa in Massive Transfusion Mannucci et al. Vox Sang 42(3):113-23 (1982) “Standard schemas involving the administration of platelet concentrates and/or fresh-frozen plasma without evaluation of hemostasis … failed to decrease the requirements for … packed red cells. Therefore, indiscriminate administration in the massively transfused postoperative patient of blood components based on preestablished schemes appears to be unjustified.” www.milblood.mil

  27. Current Practice with Plasma • More aggressive? earlier • Agrees with traditional guidelines: • Apply aggressive strategy for patients that present with coagulopathy • Is treating bleeding assoc with abnl lab • Apparent conflict with guidelines (ratio, routine schedule), but not if there is evidence of coagulopathy www.milblood.mil

  28. Evidence Supporting use of1:1 Ratio RBC:plasma • Borgman, MA. J Trauma 2007 • Retrospective study • Stratified patients by ratio of plasma:rbc • Improved outcome with higher plasma proportion www.milblood.mil

  29. Mortality % RBC:FFP ratio Recent Evidence, Plasma (Borgman, MA. J Trauma 2007) www.milblood.mil Slide courtesy JG Perkins

  30. Evidence Supporting use of Apheresis Platelets • Retrospective study pts at Ibn Sina • Received 10 or more rbcs/FWB • Compare groups: • Did not get platelets or FWB • Received platelets and not FWB • Received FWB • Findings: www.milblood.mil

  31. Study Profile - Retrospective 8,618 Trauma Patients Arrived at CSH 2,024 (23%) Received Blood Transfusions 708 (8.2%) Received ≥ 10 u Blood (RBC + FWB) in 24 hours 12 MT occurred during hospital course, not on admission 89 treated at forward surgical teams/hospitals prior to transfer to CSH 434 charts reviewed for analysis 285 Platelets – either as FWB or aPLT 149 No FWB or aPLT 23 Both FWB and aPLT 78 FWB 184 aPLT Time Period: January 2004 – December 2006 CSH = Combat Support Hospital, RBC = red blood cell, FWB = fresh whole blood, aPLT = apheresis platelets, MT = massive transfusion

  32. P<0.001 p=0.04 Log Rank p=0.003 48 Hour and 30 Day Survival by Platelet versus No Platelet Groups www.milblood.mil

  33. p=0.72 p=0.87 Log Rank p=0.96 48 Hour and 30 Day Survival by Fresh Whole Blood versus Apheresis Platelet Subgroups www.milblood.mil

  34. www.milblood.mil

  35. Factor VII Use • rFVIIa (NovoSeven) • Hemophiliac with anti-VIII (approved for) • Coumadin reversal • Stroke • Massive transfusion www.milblood.mil

  36. Factor VII Use and Outcome in OIF1 of 2 • Jan04 – Oct05, records for 61 of 117 patients who rec’d FVIIa • Groups: • Early (FVIIa before 8 units blood) • Late (after 8 units) • Groups similar for severity of injuries - Perkins, JG. J Trauma, 2007 May;62(5):1095-9 www.milblood.mil

  37. Factor VII Use and Outcome in OIF 2 of 2 • Early group rec’d fewer units of blood (20.6 vs. 25.7, p=0.048) and pRBC (16.7 vs. 21.7, p=0.049) • Similar outcomes • Mortality (33.3% vs. 34.2%, p=NS) • ARDS (5.9 vs. 6.8%, p=NS) • Infection (5.9% vs. 9.1%, p=NS) • Thrombotic events (0% vs. 2.3%, p=NS) www.milblood.mil

  38. Conclusions Regarding Blood Therapy in Massive Transfusion For select patients with coagulopathy (7-8%) • Use of either FWB or aPLT is associated with improved survival at 48 hrs and 30 days • FWB and aPLT appear equivalent with regards to survival • FFP:RBC ratios 1:2 to 1:1 are associated with improved survival at 48 hours, though this survival benefit is not apparent at 30 days. • FVIIa use might reduce red cell with no appreciable excess adverse outcome www.milblood.mil

  39. Is Old Blood Bad Blood? • “Age:” duration of storage • Storage lesion • Decreased pH • Increased K+ • Decreased 2,3-DPG • Decreased deformability • Clinical outcomes worse? (or not) www.milblood.mil

  40. Age of Blood: the Evidence • Retrospective • Inconsistent definition of age • Different preservatives, modifications • Inconsistent findings • Uniform or near uniform findings/conclusions: • Number of units is associated with worse outcome • Findings are insufficient to recommend routine use of “young” units www.milblood.mil

  41. Age of Blood: the Evidence Basran Anesth Analg 2006;103:15–20 • Retrospective, 321 re-do CABG pts • Measures of age: mean; oldest unit • Findings: correlates with longer LOS, mortality • Conclusions: should be studied with RCT before informing practice www.milblood.mil

  42. Age of Blood: the Evidence Vamvakas Transfusion 1999;39:701-710 • Retrospective, 269 cardiac surgery pts • Measures of age: mean; • Findings: age correlates with pneumonia, not with wound infection • Conclusions: should be studied with RCT before guiding transfusion policy www.milblood.mil

  43. Age of Blood: the Evidence Vamvakas Transfusion 2000;40:101-109 • Retrospective, 268 cardiac surgery pts • Measures of age: mean; oldest; 2 oldest • Findings: age does not correlate with LOS, time on ventilator • Conclusions: future studies of transfusion should consider age www.milblood.mil

  44. Age of Blood: the Evidence Keller J Trauma 2002;53:1023–1025 • Retrospective registry 18 hospitals, 86 trauma pts who rec’d 1-4 units • Measures of age: mean; oldest; 2 oldest; number >7d; >14d; >21d; >28d • Findings: only number of units >14d correlated with total LOS, not with ICU stay or vent • Conclusions: further study needed www.milblood.mil

  45. Age of Blood: the Evidence Leal-Noval Anesthesiology 2003;98:815-22 • Prospective cohort, 585 cardiac surgery pts • Measures of age: mean; oldest; youngest • Findings: • age does not correlate with LOS, time on ventilator, MI • Oldest unit and youngest unit correlates with pneumonia • Conclusions: age does not increase morbity except maybe pneumonia (number of units) www.milblood.mil

  46. Age of Blood: the Evidence Van de Watering Transfusion2006;46:1712-1718 • Retrospective, 2732 cardiac surgery pts • Measures of age: mean; oldest; youngest; comparisons for patients with all units < 18d vs all units > 18d • Findings: age correlates with number; no correlation with outcome • Conclusions: there is no justification for limitation of storage time www.milblood.mil

  47. Age of Blood: the Evidence Walsh Crit Care Med 2004; 32(2):364 –371 • Randomized ControlledTrial, 22 critical pts • Comparison: ≤5d vs ≥20d • Findings: age has no adverse effect on gastric function or measures of global oxygenation • Conclusions: no support for the use of fresh red cells in critically ill patients www.milblood.mil

  48. Summary • Current resucitation emphasizes early control of bleeding, later correction of injury • Aggressive plasma transfusion is probably best practice for coagulopathic bleeding patient • Component therapy better than FWB • FWB as good when component therapy not available • rFVII may be helpful in reducing red cell use • We will do our patients more good (or at least less harm) by reducing number of units compared with reducing age of units www.milblood.mil

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