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Shock and Coagulopathy

  • Jeffrey N. Harr
  • Fredric M. Pieracci
  • Ernest E. Moore
Chapter

Abstract

The care of bleeding trauma patients with associated orthopedic injuries remains challenging. The combination of shock and tissue injury in these severely injured patients results in multiple proinflammatory factors being released and/or produced. Unfortunately, these responses to severe injury lead to excessive inflammation resulting in worse outcomes, including multiple organ failure and death. As our understandings of post-injury physiological responses evolve, we are finding that there are multiple intersections between both the inflammatory and coagulation pathways, which explain the close and frequent association of shock with coagulopathy. However, the current evaluation and diagnosis of coagulopathies, as determined by plasma-based laboratory tests, have been limited in identifying both hypocoagulable and hypercoagulable states in post-injury trauma patients. Consequently, viscoelastic hemostatic assays are now the standard of care in identifying post-injury coagulopathies and have further elucidated links between inflammation and coagulation. Moreover, viscoelastic hemostatic assays may also prove to be the optimal devices to guide component resuscitation. Extensive research in resuscitation and the use of rapid point-of-care assays are necessary to further understand the complex pathophysiological responses to shock, especially in the trauma setting. Earlier, and appropriate, interventions, which minimize inflammation and decrease coagulopathies, may ultimately reduce transfusions and improve outcomes.

Keywords

Trauma Patient Cardiogenic Shock Disseminate Intravascular Coagulation Cerebral Perfusion Pressure Hemorrhagic Shock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Temkin O. Galenism: rise and decline of a medical philosophy. Ithaca: Cornell University Press; 1973.Google Scholar
  2. 2.
    O’Malley CD. Andreas Vesalius of Brussels, 1514–1564. Berkeley: University of California Press; 1964.Google Scholar
  3. 3.
    Power D. William Harvey. London: T. Fisher Unwin; 1897.Google Scholar
  4. 4.
    Hales S. Statistical essays: containing Haemastaticks: or an account of some hydraulic and hydrostatical experiments made on the blood and blood vessels of animals. 2nd ed. London: Innys and Others; 1740. p. 5.Google Scholar
  5. 5.
    Le Dran HF. A treatise, or reflections drawn from practice on gunshot wounds (translated). London: Clarke; 1743.Google Scholar
  6. 6.
    Gross S. A system of surgery: pathologic, diagnostic, therapeutic and operative. Philadelphia: Lea and Febiger; 1872.Google Scholar
  7. 7.
    Bernard C. Lecons sur les phenomenes de la cummuns aux animauxet aux vegetaux. Paris: JB Ballierve; 1879. p. 4.Google Scholar
  8. 8.
    Cannon W. Traumatic shock. New York: D. Appleton and Co; 1923.Google Scholar
  9. 9.
    Blalock A. Principles of surgical care, shock and other problems. St. Louis: CV Mosby; 1940.Google Scholar
  10. 10.
    Wigers HC, Ingraham RC. Hemorrhagic shock: definition and criteria for its diagnosis. J Clin Invest. 1946;25(1):30–6.Google Scholar
  11. 11.
    Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull. 2004;70:71–86.PubMedGoogle Scholar
  12. 12.
    Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357(11):1121–35.PubMedGoogle Scholar
  13. 13.
    Ogawa S, Koga S, Kuwabara K, Brett J, Morrow B, Morris SA, Bilezikian JP, Silverstein SC, Stern D. Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular camp levels. Am J Physiol. 1992;262(3 Pt 1):C546–54.PubMedGoogle Scholar
  14. 14.
    Hotchkiss RS, Strasser A, McDunn JE, Swanson PD. Cell death. N Engl J Med. 2009;361(16):1570–83.PubMedGoogle Scholar
  15. 15.
    Eltzschig HK, Eckle T. Ischemia and reperfusion—from mechanism to translation. Nat Med. 2011;17(11):1391–401.PubMedGoogle Scholar
  16. 16.
    Matzinger P. The danger model: a renewed sense of self. Science. 2002;296(5566):301–5.PubMedGoogle Scholar
  17. 17.
    Nathan C. Points of control in inflammation. Nature. 2002;420(6917):846–52.PubMedGoogle Scholar
  18. 18.
    Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190:255–66.PubMedGoogle Scholar
  19. 19.
    Stahel PH, Smith WR, Moore EE. Role of biological modifiers regulating the immune response after trauma. Injury. 2007;38(12):1409–22.PubMedGoogle Scholar
  20. 20.
    Kapur MM, Jain P, Gidh M. The effect of trauma on serum C3 activation and its correlation with injury severity score in man. J Trauma. 1986;26(5):464–6.PubMedGoogle Scholar
  21. 21.
    Kapur MM, Jain P, Gidh M. Estimation of serum complement and its role in management of trauma. World J Surg. 1988;12(2):211–6.PubMedGoogle Scholar
  22. 22.
    Younger JG, Sasaki N, Waite MD, Murray HN, Saleh EF, Ravage ZB, Hirshl RB, Ward PA, Till GO. Detrimental effects of complement activation in hemorrhagic shock. J Appl Physiol. 2001;90(2):441–6.PubMedGoogle Scholar
  23. 23.
    Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785–97.PubMedGoogle Scholar
  24. 24.
    Ioannou A, Dalle Lucca J, Tsokos GC. Immunopathogenesis of ischemia/reperfusion-associated tissue damage. Clin Immunol. 2011;141(1):3–14.PubMedGoogle Scholar
  25. 25.
    Neher MD, Weckbach S, Flierl MA, Huber-Lang MS, Stahel PF. Molecular mechanisms of inflammation and tissue injury after major trauma—is complement the “bad guy”? J Biomed Sci. 2011;18:90.PubMedGoogle Scholar
  26. 26.
    Haas PJ, van Strijp J. Anaphylatoxins: their role in bacterial infection and inflammation. Immunol Res. 2007;37(3):161–75.PubMedGoogle Scholar
  27. 27.
    Ward PA. The dark side of C5a in sepsis. Nat Rev Immunol. 2004;4(2):133–42.PubMedGoogle Scholar
  28. 28.
    Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol. 2005;23:821–52.PubMedGoogle Scholar
  29. 29.
    Spitzer D, Mitchell LM, Atkinson JP, Hourcade DE. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol. 2007;179(4):2600–8.PubMedGoogle Scholar
  30. 30.
    Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, Gebhard F, Younger JG, Drouin SM, Wetsel RA, Ward PA. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med. 2006;12(6):682–7.PubMedGoogle Scholar
  31. 31.
    Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Bruckner UB, Nilsson UB, Gebhard F, Lambris JD, Huber-Lang M. Molecular intercommunication between the complement and coagulation system. J Immunol. 2010;185(9):5628–36.PubMedGoogle Scholar
  32. 32.
    McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330(6002):362–6.PubMedGoogle Scholar
  33. 33.
    Moraes TJ, Zurawska JH, Downey GP. Neutrophil granule contents in the pathogenesis of lung injury. Curr Opin Hematol. 2006;13(1):21–7.PubMedGoogle Scholar
  34. 34.
    Buczek-Thomas JA, Lucey EC, Stone PJ, Chu CL, Rich CB, Carreras I, Goldstein RH, Foster JA, Nugent MA. Elastase mediates the release of growth factors from lung in vivo. Am J Respir Cell Mol Biol. 2004;31(3):344–50.PubMedGoogle Scholar
  35. 35.
    Chen HC, Lin HC, Liu CY, Wang CH, Hwang T, Huang TT, Lin CH, Kuo HP. Neutrophil elastase induces IL-8 synthesis by lung epithelial cells via the mitogen-activated protein kinase pathway. J Biomed Sci. 2004;11:49–58.PubMedGoogle Scholar
  36. 36.
    Steinberg J, Halter J, Schiller HJ, Dasilva M, Landas S, Gatto LA, Maisi P, Sorsa T, Rajamaki M, Lee HM, Nieman GF. Metalloproteinases inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats. J Surg Res. 2003;111(2):185–95.PubMedGoogle Scholar
  37. 37.
    Plitas G, Gagne PJ, Muhs BE, Ianus IA, Shaw JP, Beudjekian M, Delgado Y, Jacobowitz G, Rockman C, Shamamian P. Experimental hindlimb ischemia increases neutrophil-mediated matrix metalloproteinase activity: a potential mechanism for lung injury after limb ischemia. J Am Coll Surg. 2003;196(5):761–7.PubMedGoogle Scholar
  38. 38.
    Owen CA, Hu Z, Lopez-Otin C, Shapiro SD. Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase. J Immunol. 2004;172(12):7791–803.PubMedGoogle Scholar
  39. 39.
    Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, Eriksson EE, Herwald H, Agerberth B, Lindbom L. Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest. 2008;118(10):3491–502.PubMedGoogle Scholar
  40. 40.
    Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005;77(5):598–625.PubMedGoogle Scholar
  41. 41.
    Usatyuk PV, Nataajan V. Regulation of reactive oxygen species-induced endothelial cell-cell and cell-matrix contacts by focal adhesion kinase and adherens junction proteins. Am J Physiol Lung Cell Mol Physiol. 2005;289(6):L999–1010.PubMedGoogle Scholar
  42. 42.
    Scheel-Toellner D, Wang K, Assi LK, Webb PR, Braddock RM, Salmon M, Lord JM. Clustering of death receptors in lipid rafts initiates neutrophil spontaneous apoptosis. Biochem Soc Trans. 2004;32(Pt 5):679–81.PubMedGoogle Scholar
  43. 43.
    Moore EE, Moore FA, Harken AH, Johnson JL, Ciesla D, Banerjee A. The two-event construct of postinjury multiple organ failure. Shock. 2005;24 Suppl 1:71–4.PubMedGoogle Scholar
  44. 44.
    Rhoades RA, Bell DR, editors. Medical physiology: principles for clinical medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2012.Google Scholar
  45. 45.
    Irwin RS, Rippe JM, editors. Intensive care medicine. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.Google Scholar
  46. 46.
    Holcomb JB. Damage control resuscitation. J Trauma. 2007;62(6 Suppl):S36–7.PubMedGoogle Scholar
  47. 47.
    Cotton BA, Reddy N, Hatch QM, LeFebvre E, Wade CE, Kozar RA, Gill BS, Albarado R, McNutt MK, Holcomb JB. Damage control resuscitation is associated with a reduction in resuscitation volume and improvement in survival in 390 damage control laparotomy patients. Ann Surg. 2011;254(4):598–605.PubMedGoogle Scholar
  48. 48.
    Brenner M, Stein DM, Hu PF, Aarabi B, Sheth K, Scalea TM. Traditional systolic blood pressure targets underestimate hypotension-induced secondary brain injury. J Trauma Acute Care Surg. 2012;72(5):1135–9.PubMedGoogle Scholar
  49. 49.
    Bratton SL, Chestnut GM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma. 2007;24:S59–64.PubMedGoogle Scholar
  50. 50.
    Robertson CS, Baladka AB, Hannay HJ, Contant CF, Gopinath SP, Cormio M, Uzura M, Grossman RG. Prevention of secondary ischemic insults after severe head injury. Crit Care Med. 1999;27(10):2086–95.PubMedGoogle Scholar
  51. 51.
    Human albumin administration in critically ill patients: systematic review of randomized controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ. 1998;317(7153):235–40.Google Scholar
  52. 52.
    Roberts I, Blackhall K, Alderson P, Bunn F, Schierhout G. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2011;(11):CD001208.Google Scholar
  53. 53.
    Lissauer ME, Chi A, Kramer ME, Scalea TM, Johnson SB. Association of 6% hetastarch resuscitation with adverse outcomes in critically ill trauma patients. Am J Surg. 2011;202(1):53–8.PubMedGoogle Scholar
  54. 54.
    Avorn J, Patel M, Levin R, Winkelmayer WC. Hetastarch and bleeding complications after coronary artery surgery. Chest. 2003;124(4):1437–42.PubMedGoogle Scholar
  55. 55.
    Bulger EM, May S, Kerby JD, Emeron S, Stiell IG, Schreiber MA, Brasel KJ, Tisherman SA, Coimbra R, Rizoli S, Minei JP, Hata JS, Sopko G, Evans DC, Hoyt DB. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011;253(3):431–41.PubMedGoogle Scholar
  56. 56.
    Mann DV, Robinson MK, Rounds JD, DeRosa E, Niles DA, Ingwall JS, Wilmore DW, Jacobs DO. Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study. Ann Surg. 1997;226(5):653–61.PubMedGoogle Scholar
  57. 57.
    Scalea TM, Maltz S, Yelon J, Trooskin SZ, Duncan AO, Sclafani SJ. Resuscitation of multiple trauma and head injury: role of crystalloid fluids and inotropes. Crit Care Med. 1994;22(10):1610–5.PubMedGoogle Scholar
  58. 58.
    Abou-Khalil B, Scalea TM, Trooskin SZ, Henry SM, Hitchcock R. Hemodynamic responses to shock in young trauma patients; need for invasive monitoring. Crit Care Med. 1994;22(4):633–9.PubMedGoogle Scholar
  59. 59.
    Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH. Physiologic patterns in surviving and nonsurviving shock patients; use of sequential cardiorespiratory variables in defining criteria for therapeutic goals and early warning of death. Arch Surg. 1973;106(5):630–6.PubMedGoogle Scholar
  60. 60.
    Shoemaker WC, Appel P, Bland R. Use of physiologic monitoring to predict outcome and to assist in clinical decisions in critically ill postoperative patients. Am J Surg. 1983;146(1):43–8.PubMedGoogle Scholar
  61. 61.
    Fleming A, Bishop M, Shoemaker W, Appel P, Sufficool W, Kuvhenguwha A, Kennedy F, Wo CJ. Prospective trial of supranormal values as goals of resuscitation in severe trauma. Arch Surg. 1992;127(10):1175–81.PubMedGoogle Scholar
  62. 62.
    Bishop MH, Shoemaker WC, Appel PL, Meade P, Ordog GJ, Wasserberger J, Wo CJ, Rimle DA, Kram HB, Umali R, Kennedy F, Shuleshko J, Stephen CM, Shori SK, Thadepalli HD. Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma. J Trauma. 1995;38(5):780–7.PubMedGoogle Scholar
  63. 63.
    Moore FA, Haenel JB, Moore EE, Whitehill TA. Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multisystem organ failure. J Trauma. 1992;33(1):58–67.PubMedGoogle Scholar
  64. 64.
    Durham RM, Neunaber K, Mazuski JE, Shapiro MJ, Baue AE. The use of oxygen consumption and delivery as endpoints for resuscitation in critically ill patients. J Trauma. 1996;41(1):32–40.PubMedGoogle Scholar
  65. 65.
    Velmahos GC, Demetriades D, Shoemaker WC, Chan LS, Tatevossian R, Wo CC, Vassiliu P, Cornwell 3rd EE, Murray JA, Roth B, Belzberg H, Asensio JA, Berne TV. Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial. Ann Surg. 2000;232(3):409–18.PubMedGoogle Scholar
  66. 66.
    McKinley BA, Kozar RA, Cocanour CS, Baldivia A, Sailors RM, Ware DN, Moore FA. Normal versus supranormal oxygen delivery goals in shock resuscitation: the response is the same. J Trauma. 2002;53(5):825–32.PubMedGoogle Scholar
  67. 67.
    Balogh Z, McKinley BA, Cocanour CS, Kozar RA, Valdivia A, Sailors RM, Moore FA. Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome. Arch Surg. 2003;138(6):637–42.PubMedGoogle Scholar
  68. 68.
    Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med. 1995;333(16):1025–32.PubMedGoogle Scholar
  69. 69.
    Sauaia A, Moore FA, Moore EE, Haenel JB, Read RA, Lezotte DC. Early predictors of postinjury multiple organ failure. Arch Surg. 1994;129(1):39–45.PubMedGoogle Scholar
  70. 70.
    Kincaid EH, Miller PR, Meredith JW, Rahman N, Chang MC. Elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization. J Am Coll Surg. 1998;187(4):384–92.PubMedGoogle Scholar
  71. 71.
    Rixen D, Raum M, Bouillon B, Lefering R, Neugebauer E. Base deficit development and its prognostic significance in posttrauma critical illness: an analysis by the trauma registry of the Deutsche Gesellschaft Fur unfallchirurgi. Shock. 2001;15(2):83–9.PubMedGoogle Scholar
  72. 72.
    Vincent J-L, Dufaye P, Berre J, Leeman M, Degaute J-P, Kahn RJ. Serial lactate determinations during circulatory shock. Crit Care Med. 1983;11:449–51.PubMedGoogle Scholar
  73. 73.
    Doglio GR, Pusajo JF, Egurrola MA, Bonfigili GC, Parra C, Vetere L, Hernandez MS, Fernandez S, Palizas F, Guiterrez G. Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med. 1991;19(8):1037–40.PubMedGoogle Scholar
  74. 74.
    Maynard N, Bihari D, Beale R, Smithies M, Baldock G, Mason R, McColl I. Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure. JAMA. 1993;270(10):1203–10.PubMedGoogle Scholar
  75. 75.
    Chang MC, Meredith JW. Cardiac preload, splanchnic perfusion, and their relationship during resuscitation in trauma patients. J Trauma. 1997;42(4):577–82.PubMedGoogle Scholar
  76. 76.
    Soller BR, Cingo N, Puyana JC, Khan T, His C, Kim H, Favreau J, Heard SO. Simultaneous measurement of hepatic tissue pH, venous oxygen saturation and hemoglobin by near infrared spectroscopy. Shock. 2001;15(2):106–11.PubMedGoogle Scholar
  77. 77.
    Soller BR, Heard SO, Cingo NA, His C, Favreau J, Khan T, Ross RR, Puyana JC. Application of fiberoptic sensors for the study of hepatic dysoxia in swine hemorrhagic shock. Crit Care Med. 2001;29(7):1438–44.PubMedGoogle Scholar
  78. 78.
    Sims C, Seigne P, Menconi M, Monarca J, Barlow C, Pettit J, Puyana JC. Skeletal muscle acidosis correlates with the severity of blood volume loss during shock and resuscitation. J Trauma. 2001;51(6):1137–46.PubMedGoogle Scholar
  79. 79.
    Beekley AC, Martin MJ, Nelson T, Grathwohl KW, Griffith M, Beilman G, Holcomb JB. Continuous noninvasive tissue oximetry in the early evaluation of the combat casualty: a prospective study. J Trauma. 2010;69 Suppl 1:S14–25.PubMedGoogle Scholar
  80. 80.
    Roumen RM, Redl H, Schlag G, Zilow G, Sandtner W, Koller W, Hendriks T, Goris RJ. Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. Crit Care Med. 1995;23(3):474–80.PubMedGoogle Scholar
  81. 81.
    Lenz A, Franklin GA, Cheadle WG. Systemic inflammation after trauma. Injury. 2007;38(12):1336–45.PubMedGoogle Scholar
  82. 82.
    Gebhard F, Pfetsch H, Steinbach G, Strecker W, Kinzl L, Bruckner UB. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch Surg. 2000;135(3):291–5.PubMedGoogle Scholar
  83. 83.
    Harris HE, Raucci A. Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep. 2006;7(8):774–8.PubMedGoogle Scholar
  84. 84.
    Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol. 2005;17(4):359–65.PubMedGoogle Scholar
  85. 85.
    Manson J, Thiemermann C, Brohi K. Trauma alarmins as activators of damage-induced inflammation. Br J Surg. 2012;99 Suppl 1:12–20.PubMedGoogle Scholar
  86. 86.
    Cohen MJ, Brohi K, Calfee CS, Rahn P, Chesebro BB, Christiaans SC, Carles M, Howard M, Pittet JF. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Crit Care. 2009;13(6):R174.PubMedGoogle Scholar
  87. 87.
    Pespeni M, Mackersie RC, Lee H, Morabito D, Hodnett M, Howard M, Pittet JF. Serum levels of Hsp60 correlate with the development of acute lung injury after trauma. J Surg Res. 2005;126(1):41–7.PubMedGoogle Scholar
  88. 88.
    Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–7.PubMedGoogle Scholar
  89. 89.
    Leclerc E, Fritz G, Vetter SW, Heizmann CW. Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta. 2009;1793(6):993–1007.PubMedGoogle Scholar
  90. 90.
    Hayakata T, Shiozaki T, Tasaki O, Ikegawa H, Inoue Y, Toshiyuki F, Hosotubo H, Kieko F, Yamashita T, Tanaka H, Shimazu T, Sugimoto H. Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury. Shock. 2004;22(2):102–7.PubMedGoogle Scholar
  91. 91.
    Vos PE, Jacobs B, Andriessen TM, Lamers KJ, Borm GF, Beems T, Edwards M, Rosmalen CF, Vissers JL. GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology. 2010;75(20):1786–93.PubMedGoogle Scholar
  92. 92.
    Galichet A, Weibel M, Heizmann CW. Calcium-regulated intramembrane proteolysis of the RAGE receptor. Biochem Biophys Res Commun. 2008;370(1):1–5.PubMedGoogle Scholar
  93. 93.
    Cohen MJ, Carles M, Brohi K, Calfee CS, Rahn P, Call MS, Chesebro BB, West MA, Pittet JF. Early release of soluble receptor for advanced glycation endproducts after severe trauma in humans. J Trauma. 2010;68(6):1273–8.PubMedGoogle Scholar
  94. 94.
    Johnson GB, Brunn GJ, Platt JL. Cutting edge: an endogenous pathway to systemic inflammatory response syndrome (SIRS)-like reactions through Toll-like receptor 4. J Immunol. 2004;172(1):20–4.PubMedGoogle Scholar
  95. 95.
    Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581–90.PubMedGoogle Scholar
  96. 96.
    Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345(8):588–95.PubMedGoogle Scholar
  97. 97.
    Angus DC, Linde-Zwirble WT, Lidicker J. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10.PubMedGoogle Scholar
  98. 98.
    Dombrovskiy VY, Martin AA, Sunderram J. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993–2003. Crit Care Med. 2007;35:1414–5.Google Scholar
  99. 99.
    Fortin CF, McDonald PP, Fulop T, Lesur O. Sepsis, leukocytes, and nitric oxide (NO): an intricate affair. Shock. 2010;33(4):344–52.PubMedGoogle Scholar
  100. 100.
    Castellanos-Ortega A, Suberviola B, Garcia-Astudillo LA, Holanda MS, Ortiz F, Llorca J, Delgado-Rodriquez M. Impact of the surviving sepsis campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. Crit Care Med. 2010;38(4):1036–43.PubMedGoogle Scholar
  101. 101.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327.PubMedGoogle Scholar
  102. 102.
    Furlan JC, Fehlings MG. Cardiovascular complications after acute spinal cord injury: pathophysiology, diagnosis, and management. Neurosurg Focus. 2008;25(5):E13.PubMedGoogle Scholar
  103. 103.
    Garstang SV, Miller-Smith SA. Autonomic nervous system dysfunction after spinal cord injury. Phys Med Rehabil Clin N Am. 2007;18(2):275–96.PubMedGoogle Scholar
  104. 104.
    Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine. 2001;26(24 Suppl):S2–12.PubMedGoogle Scholar
  105. 105.
    Guly HR, Bouamra O, Lecky FE. The incidence of neurogenic shock in patients with isolated spinal cord injury in the emergency department. Resuscitation. 2008;76(1):57–62.PubMedGoogle Scholar
  106. 106.
    Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc. 2009;84(9):822–30.PubMedGoogle Scholar
  107. 107.
    Levi L, Wolf A, Belzberg H. Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome. Neurosurgery. 1993;33(6):1007–16.PubMedGoogle Scholar
  108. 108.
    Hadley MN, Walters BC, Grabb PA, Oyesiku NM, Przybylski GJ, Resnick DK, Ryken TC, Mielke DH. Guidelines for the management of acute cervical spine and spinal cord injuries. Neurosurgery. 2002;49:407–98.Google Scholar
  109. 109.
    King BS, Gupta R, Narayan RK. The early assessment and intensive care unit management of patients with severe traumatic brain and spinal cord injuries. Surg Clin North Am. 2000;80(3):855–70, viii–ix.PubMedGoogle Scholar
  110. 110.
    Stevens RD, Bhardwaj A, Kirsch JR, Mirski MA. Critical care and perioperative management in traumatic spinal cord injury. J Neurosurg Anesthesiol. 2003;15(3):215–29.PubMedGoogle Scholar
  111. 111.
    Hollenberg SM, Kavinsky CJ, Parrillo JE. Cardiogenic shock. Ann Intern Med. 1999;131(1):47–59.PubMedGoogle Scholar
  112. 112.
    Patel AK, Hollenberg SM. Cardiovascular failure and cardiogenic shock. Semin Respir Crit Care Med. 2011;32(5):598–606.PubMedGoogle Scholar
  113. 113.
    Hollenberg SM. Cardiogenic shock. Crit Care Clin. 2001;17(2):391–410.PubMedGoogle Scholar
  114. 114.
    Becker RC. Hemodynamic, mechanical, and metabolic determinants of thrombolytic efficacy: a theoretic framework for assessing the limitations of thrombolysis in patients with cardiogenic shock. Am Heart J. 1993;125(3):919–29.PubMedGoogle Scholar
  115. 115.
    Leigh-Smith S, Harris T. Tension pneumothorax—time for a re-think? Emerg Med J. 2005;22(1):8–16.PubMedGoogle Scholar
  116. 116.
    Bodson L, Bouferrache K, Vieillard-Baron A. Cardiac tamponade. Curr Opin Crit Care. 2011;17(5):416–24.PubMedGoogle Scholar
  117. 117.
    Fowler NO, Holmes JC. Hemodynamic effects of isoproterenol and norepinephrine in acute cardiac tamponade. J Clin Invest. 1969;48(3):502–7.PubMedGoogle Scholar
  118. 118.
    Yee ES, Verrier ED, Thomas AN. Management of air embolism in blunt and penetrating thoracic trauma. J Thorac Cardiovasc Surg. 1983;85(5):661–8.PubMedGoogle Scholar
  119. 119.
    Trunkey D. Initial treatment of patients with extensive trauma. N Engl J Med. 1991;324(18):1259–63.PubMedGoogle Scholar
  120. 120.
    Krug EG, Sharma GK, Lozana R. The global burden of injuries. Am J Public Health. 2000;90(4):523–6.PubMedGoogle Scholar
  121. 121.
    Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, Pons PT. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185–93.PubMedGoogle Scholar
  122. 122.
    Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127–30.PubMedGoogle Scholar
  123. 123.
    Macleod JBA, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55(1):39–44.PubMedGoogle Scholar
  124. 124.
    Maegele M, Lefering R, Yucel N, Tjardes T, Rixen D, Paffrath T, Simanski C, Neugebauer E, Bouillon B. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38(3):298–304.PubMedGoogle Scholar
  125. 125.
    Stefanini M. Basic mechanisms of hemostasis. Bull N Y Acad Med. 1954;30(4):239–77.PubMedGoogle Scholar
  126. 126.
    Kshuk JL, Moore EE, Millikan JS, Moore JB. Major abdominal vascular trauma—a unified approach. J Trauma. 1982;22(8):672–9.Google Scholar
  127. 127.
    Harrigan C, Lucas CE, Ledgerwood AM. The effect of hemorrhagic shock on the clotting cascade in injured patients. J Trauma. 1989;29(10):1416–21.PubMedGoogle Scholar
  128. 128.
    Phillips TF, Soulier G, Wilson RF. Outcome of massive transfusion exceeding two blood volumes in trauma and emergency surgery. J Trauma. 1987;27(8):903–10.PubMedGoogle Scholar
  129. 129.
    Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007;245(5):812–8.PubMedGoogle Scholar
  130. 130.
    Hoffman M, Monroe DM. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958–65.PubMedGoogle Scholar
  131. 131.
    Falati S, Gross P, Merrill-Skoloff G, Furie BC, Furie B. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med. 2002;8(10):1175–81.PubMedGoogle Scholar
  132. 132.
    Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci. 2001;936:291–311.PubMedGoogle Scholar
  133. 133.
    Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activatable fibrinolysis inhibitor. J Biol Chem. 1995;270(24):14477–84.PubMedGoogle Scholar
  134. 134.
    Ofosu FA. Protease activated receptors 1 and 4 govern the responses of human platelets to thrombin. Transfus Apher Sci. 2003;28(3):265–8.PubMedGoogle Scholar
  135. 135.
    Cannon WB, Fraser J, Cowell E. The preventive treatment of wound shock. JAMA. 1918;70(9):618–21.Google Scholar
  136. 136.
    Kashuk JL, Moore EE, Sawyer M, Wohlauer M, Pezold M, Barnett C, Biffl WL, Burlew CC, Johnson JL, Sauaia A. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg. 2010;252(3):434–42.PubMedGoogle Scholar
  137. 137.
    Cohen MJ, Call M, Nelson M, Calfee CS, Esmon CT, Brohi K, Pittet JF. Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann Surg. 2012;255(2):379–85.PubMedGoogle Scholar
  138. 138.
    Gando S. Acute coagulopathy of trauma shock and coagulopathy of trauma: a rebuttal. You are now going down the wrong path. J Trauma. 2009;67(2):381–3.PubMedGoogle Scholar
  139. 139.
    Hardaway RM. The significance of coagulative and thrombotic changes after haemorrhage and injury. J Clin Pathol Suppl (R Coll Pathol). 1970;4:110–20.Google Scholar
  140. 140.
    Gando S, Nakanishi Y, Tedo I. Cytokines and plasminogen activator inhibitor-I in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction syndrome. Crit Care Med. 1995;23(11):1835–42.PubMedGoogle Scholar
  141. 141.
    Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191–5.PubMedGoogle Scholar
  142. 142.
    Kooistra T, Schrauwen Y, Arts J, Emeis JJ. Regulation of endothelial cell t-PA synthesis and release. Int J Hematol. 1994;59(4):233–55.PubMedGoogle Scholar
  143. 143.
    Wohlauer MV, Moore EE, Thomas S, Sauaia A, Evans E, Harr J, Silliman CC, Ploplis V, Castellino FJ, Walsh M. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012;214(5):739–46.PubMedGoogle Scholar
  144. 144.
    Davenport R, Curry N, Manson J, De’Ath H, Coates A, Rourke C, Pearse R, Stanworth S, Brohi K. Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2. J Trauma. 2011;70(1):90–5.PubMedGoogle Scholar
  145. 145.
    Advanced trauma life support for doctors. 9th ed. Chicago: American College of Surgeons; 2012.Google Scholar
  146. 146.
    Kashuk JL, Moore EE, Johnson JL, Haenel J, Wilson M, Moore JB, Cothren CC, Biffl WL, Banerjee A, Sauaia A. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma: packed red blood cells the answer? J Trauma. 2008;65(2):261–70.PubMedGoogle Scholar
  147. 147.
    Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007;63(4):805–13.PubMedGoogle Scholar
  148. 148.
    Duchesne JC, Hunt JP, Wahl G, Marr AB, Wang YZ, Weintraub SE, Wright MJ, McSwain Jr NE. Review of current blood transfusions strategies in a mature level I trauma center: were we wrong for the last 60 years? J Trauma. 2008;65(2):272–8.PubMedGoogle Scholar
  149. 149.
    Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper GJ, Perkins JG, Spinella PC, Williams KL, Park MS. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248(3):447–58.PubMedGoogle Scholar
  150. 150.
    Teixeira PG, Inaba K, Shulman I, Salim A, Demetriades D, Brown C, Browder T, Green D, Rhee P. Impact of plasma transfusion in massively transfused trauma patients. J Trauma. 2009;66(3):693–7.PubMedGoogle Scholar
  151. 151.
    Spinella PC, Perkins JG, Grathwohl KW, Beekley AC, Niles SE, McLaughlin DF, Wade CE, Holcomb JB. Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries. J Trauma. 2008;64(2 Suppl):S69–78.PubMedGoogle Scholar
  152. 152.
    Bick RL, Kaplan H. Syndromes of thrombosis and hypercoagulability. Congenital and acquired causes of thrombosis. Med Clin North Am. 1998;82(3):409–58.PubMedGoogle Scholar
  153. 153.
    Counts RB, Haisch C, Simon TL, Maxwell NG, Heimbach DM, Carrico CJ. Hemostasis in massively transfused trauma patients. Ann Surg. 1979;190(1):91–9.PubMedGoogle Scholar
  154. 154.
    Lucas CE, Ledgerwood AM. Clinical significance of altered coagulation tests after massive transfusion for trauma. Am Surg. 1981;47(3):125–30.PubMedGoogle Scholar
  155. 155.
    von Kaulla KN, Swan H. Clotting deviations in man associated with open-heart surgery during hypothermia. J Thorac Surg. 1958;36(6):857–68.Google Scholar
  156. 156.
    von Kaulla KN, Kaye H, von Kaulla E, Marchioro TL, Starzl TE. Changes in blood coagulation. Before and after hepatectomy or transplantation in dogs and man. Arch Surg. 1966;92(1):71–9.Google Scholar
  157. 157.
    Kheirabadi BS, Crissey JM, Deguzman R, Holcomb JB. In vivo bleeding time and in vitro thrombelastography measurements are better indicators of dilutional hypothermic coagulopathy than prothrombin time. J Trauma. 2007;62(6):1352–9.PubMedGoogle Scholar
  158. 158.
    Park MS, Martini WZ, Dubick MA, Salinas J, Butenas S, Kheirabadi BS, Pusateri AE, Vos JA, Guymon CH, Wolf SE, Mann KG, Holcomb JB. Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time. J Trauma. 2009;67(2):266–75.PubMedGoogle Scholar
  159. 159.
    Plotkin AJ, Wade CE, Jenkins DH, Smith KA, Noe JC, Park MS, Perkins JG, Holcomb JB. A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma. 2008;64(2 Suppl):S64–8.PubMedGoogle Scholar
  160. 160.
    Martini W, Cortez D, Dubick M, Park MS, Holcomb JB. Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma. 2008;65(3):535–43.PubMedGoogle Scholar
  161. 161.
    Doran CM, Woolley T, Midwinter MJ. Feasibility of using rotational thromboelastometry to assess coagulation status of combat casualties in a deployed setting. J Trauma. 2010;69 Suppl 1:S40–8.PubMedGoogle Scholar
  162. 162.
    Davenport R, Manson J, De’Ath H, Platton S, Coates A, Allard S, Hart D, Pearse R, Pasi KJ, Mac Callum P, Stanworth S, Brohi K. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med. 2011;39(12):2652–8.PubMedGoogle Scholar
  163. 163.
    Rahbar MH, Fox EE, Del Junco DJ, Cotton BA, Podbielski JM, Matijevic N, Cohen MJ, Schreiber MA, Zhang J, Mirhaji P, Duran SJ, Reynolds RJ, Benjamin-Garner R, Holcomb JB. Coordination and management of multicenter clinical studies in trauma: experience from the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Resuscitation. 2012;83(4):459–64.PubMedGoogle Scholar
  164. 164.
    Rourke C, Curry N, Khan S, Taylor R, Raza I, Davenport R, Stanworth S, Brohi K. Fibrinogen levels during trauma hemorrhage, response to replacement therapy and association with patient outcomes. J Thromb Haemost. 2012;10(7):1342–51.PubMedGoogle Scholar
  165. 165.
    Johansson PI, Stensballe J. Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets—a review of the current literature. Transfusion. 2010;50(3):701–10.PubMedGoogle Scholar
  166. 166.
    Johansson PI, Stensballe J. Effect of haemostatic control resuscitation on mortality in massively bleeding patients: a before and after study. Vox Sang. 2009;96(2):111–8.PubMedGoogle Scholar
  167. 167.
    Johansson PI. Goal-directed hemostatic resuscitation for massively bleeding patients: the Copenhagen concept. Transfus Apher Sci. 2010;43(3):401–5.PubMedGoogle Scholar
  168. 168.
    Schochl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, Kozek-Langenecker S, Solomon C. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care. 2010;14(2):R55.PubMedGoogle Scholar
  169. 169.
    Chambers LA, Chow SJ, Shaffer LE. Frequency and characteristics of coagulopathy in trauma patients treated with a low- or high-plasma-content massive transfusion protocol. Am J Clin Pathol. 2011;136(3):364–70.PubMedGoogle Scholar
  170. 170.
    Schochl H, Cotton B, Inaba K, Nienaber U, Fischer H, Voelckel W, Solomon C. FIBTEM provides early prediction of massive transfusion in trauma. Crit Care. 2011;15(6):R265.PubMedGoogle Scholar
  171. 171.
    Stinger HK, Spinella PC, Perkins JG, Grathwohl KW, Salinas J, Martini WZ, Hess JR, Dubick MA, Simon CD, Beekley AC, Wolf SE, Wade CE, Holcomb JB. The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital. J Trauma. 2008;64(2 Suppl):S79–85.PubMedGoogle Scholar
  172. 172.
    Dunbar NM, Chandler WL. Thrombin generation in trauma patients. Transfusion. 2009;49(12):2652–60.PubMedGoogle Scholar
  173. 173.
    Tauber H, Innerhofer P, Breitkopf R, Westermann I, Beer R, El Attal R, Strasak A, Mittermayr M. Prevalence and impact of abnormal ROTEM assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study’. Br J Anaesth. 2011;107(3):378–87.PubMedGoogle Scholar
  174. 174.
    Schochl H, Nienaber U, Maegele M, Hochleitner G, Primavesi F, Steitz B, Arndt C, Hanke A, Voelckel W, Solomon C. Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Crit Care. 2011;15(2):R83.PubMedGoogle Scholar
  175. 175.
    Holcomb JB, Zarzabal LA, Michalex JE, Kozar RA, Spinella PC, Perkins JG, Matijevic N, Dong JF, Pati S, Wade CE, Trauma Outcomes Group, et al. Increased platelet: RBC ratios are associated with improved survival after massive transfusion. J Trauma. 2011;71(2 Suppl 3):S318–28.PubMedGoogle Scholar
  176. 176.
    Simmons JW, White CE, Eastridge BJ, Mace JE, Wade CE, Blackbourne LH. Impact of policy change on US Army combat transfusion practices. J Trauma. 2010;69 Suppl 1:S75–80.PubMedGoogle Scholar
  177. 177.
    Dirks J, Jorgensen H, Jensen CH, Ostrowski SR, Johansson PI. Blood product ratio in acute traumatic coagulopathy—effect on mortality in a Scandinavian level 1 trauma centre. Scand J Trauma Resusc Emerg Med. 2010;18:65.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jeffrey N. Harr
    • 1
  • Fredric M. Pieracci
    • 2
  • Ernest E. Moore
    • 2
  1. 1.Department of SurgeryUniversity of Colorado DenverAuroraUSA
  2. 2.Department of SurgeryDenver Health Medical Center and University of Colorado DenverDenverUSA

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