Trauma is the most common cause of death under the age of 45. Many trauma patients die of multiple organ failure, especially acute respiratory distress syndrome. The basic cause of traumatic shock has only partially been elucidated. Data resources include research papers on the subject of trauma and shock from 1875 to the present. These papers numbered more than 40,000. Almost all of the papers proposed that traumatic shock was due to hypovolemia. The concept of a shock toxin as promulgated during World War I is correct. This toxin is a thrombogenic aminophospholipid that occurs only on the inner layer of all cell membranes and is liberated by cell destruction. It causes disseminated intravascular coagulation, which may obstruct the microcirculation of any and all organs producing multiple organ failure by microclots. These microclots may be lysed by plasminogen activator and circulation to the organs restored.
Get full access to this article
View all access options for this article.
References
1.
Statistical Abstract of the United States: The National Data Book. 115th Ed. Austin, TX: Reference Press, 1995.
CollinsJA, GordonWCJr, HudsonTL, IrvinRWJr, KellyT, HardawayRMIII. Inapparent hypoxemia in casualties with wounded limbs: Pulmonary fat embolism?Ann Surg1968;167:511–20.
4.
HardawayRM. Shock lung. Int Sug1972;58:311–15.
5.
HardawayRM. Care of the Wounded in Vietnam. Manhattan, KS: Sunflower University Press, 1988.
6.
FishmanAP. Shock lung: A distinctive nonentity. Circulation1973;47:921–3.
7.
AyresSM. Mechanisms and consequences of pulmonary edema: Cardiac lung, shock lung, and principles of ventilatory therapy in adult respiratory distress syndrome. Am Heart J1982; 103:97–112.
8.
ShoemakerWC, HauserCJ. Critique of crystalloid versus colloid therapy in shock and shock lung. Crit Care Med1979;7:117–24.
9.
GeelhoedGW, BennettSH. “Shock lung” resulting from perfusion of canine lungs with stored bank blood. Am Surg1975; 41:661–82.
10.
AshbaughDC, BigelowDB, PettyTL, LevineBE. Acute respiratory distress in adults. Lancet1967;ii:319–23.
HardawayRM. Disseminated intravascular coagulation and the treatment of adult respiratory distress syndrome with plasminogen activator. Hematol Rev1994;9:3–19.
13.
The Medical Department of the United States Army in the World War: Surgery. Surgeon General, US Army, 1927.
14.
BlalockA. Experimental shock: The cause of the low blood pressure produced by muscle injury. Arch Surg1930;20:956–96.
15.
HardawayRM, WilliamsCH, MarvastiM, . Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med1990;18:1413–8.
16.
HardawayRM, JohnsonDG, HouchinDN, . The influence of extracorporeal handling of blood on hemorrhagic shock in dogs. Exp Med Surg1965;23:28–37.
17.
HardawayRMIII. Care of the wounded in the United States Army from 1775 to 1991. Surg Gynecol Obstet1992;175:74–88.
18.
TrunkeyDD. Hypovolemic, traumatic shock. In: HardawayRM, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 158–77.
19.
HardawayRM, ed. Shock: The Reversible State of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 26–8.
20.
KollefMH, SchusterDP. The acute repiratory distress syndrome. N Engl J Med1995;332:27–37.
21.
De KimpeSJ, KengatharanM, ThiemermannC, VaneJR. The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci USA1995;92:59–63.
22.
HoffmanWD, DannerRL, QuezadoZMN, . Role of endotoxemia in cardiovascular dysfunction and lethality: Virulent and nonvirulent Escherichia coli challenges in canine model of septic shock. Infect Immun1996;64:604–12.
23.
TangW, PakulaJL, WeillMH, . Adrenergic vasopressor agents and mechanical ventilation for the treatment of experimental septic shock. Crit Care Med1996;24:125–30.
24.
FaheyTJIII, YoshiokaT, ShiresGT, FantiniGA. The role of tumor necrosis factor and nitric oxide in the acute cardiovascular response to endotoxin. Ann Surg1996;223:63–9.
25.
DaikosGK. Bacterial factors in septic shock. Nephrol Dial Transplant1994;9(Suppl 4):45–6.
26.
SuffrediniAF. Current prospects for the treatment of clinical sepsis. Crit Care Med1994;22:12–88.
27.
SmithPD, SuffrediniAP, AllenJB, . Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators. J Clin Immunol1994;14:141–8.
28.
GatesDM. Cardiac dysfunction in septic shock and multiple organ dysfunction syndrome. Crit Care Nurs Q1994;16:39–48.
29.
BoneRC. Sepsis and controlled clinical trials: The odyssey continues (Editorial). Crit Care Med1995;23:1313–5.
30.
BoneRC. Sepsis and RIRS. Nephrol Dial Transplant1994;9(Suppl):90–103.
31.
KarzaiW, ReillyJM, HoffmanWD, . Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis. Am J Physiol1995;268:692–702.
32.
HoffmanWD, NatansonC. Endotoxin in septic shock. Anesth Analg1993;77:613–24.
33.
NatansonC, HoffmanWD, SuffrediniAF, . Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med1994;120:771–83.
34.
EichackerPQ, WaismanY, NatansonC, . Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis. J Appl Physiol1994;77:2366–73.
35.
WaismanTJ, NatansonC. Acute hemorrhage in dogs: Construction and validation of models to quantify blood loss. J Appl Physiol1993;74:510–9.
36.
QuezadoZM, HoffmanWD, WinkelsteinJA, . The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure. J Exp Med1994;179:569–78.
37.
DannerRL, EichackerPQ, DoerflerME, . Therapeutic trial of lipid X in a canine model of septic shock. J Infect Dis1993;167:378–84.
38.
QuezadoZM, NatansonC, BanksSM, . Therapeutic trial of reconstituted human high-density lipoprotein in a canine model of Gram-negative septic shock. J Pharmacol Exp Ther1995; 272:604–11.
NatansonC, HoffmanWD, KoevLA, . Plasma exchange does not improve survival in a canine, model of human septic shock. Transfusion1993;33:243–8.
41.
MayerJ, HajekR, VorlicekJ, TomiskaM. Sepsis and septic shock. I. Definitions and pathophysiology. Support Care Cancer1995;3:106–10.
42.
BrownKK. Critical interventions in septic shock. Am J Nurs1994;94:20–5.
43.
MayerJ, HajekR, VorlicekJ, TomishaM. Sepsis and septic shock. II. Treatment. Support Care Cancer1995;3:111–9.
44.
OlsonNC, HeliverPW, DodamJR. Mediators and vascular effects in response to endotoxin. Br Vet J1995;151:489–522.
45.
MeadowW, RudinskyB. Inflammatory mediators and neonatal sepsis: Rarely has so little been known by so many about so much. Clin Perinatol1995;22:519–36.
46.
WiessnerWH, CaseyLC, ZbilutJP. Treatment of sepsis and septic shock: A review. Heart Lung1995;24:380–93.
47.
CamussiG, MontrucchioG, DoninioniL, DionigiR. Septic shock: The unravelling of molecular mechanisms. Nephrol Dial Transplant1995;10:1808–13.
48.
MalcheskyPS, ZborowskiM, HouKC. Extracorporeal techniques of endotoxin removal: A review of the art and science. Adv Ren Replace Ther1995;2:60–9.
WolfeTA, DastaJF. Use of nitric oxide synthase inhibitors as a novel treatment for septic shock. Ann Pharmacother1995;29: 36–46.
51.
MukaidaN, IshikawaY, IkedaN, . Novel insight into molecular mechanism of endotoxin shock: Biochemical analysis of LPS receptor signaling in a cell-free system targeting NFkappa B and regulation of cytokine production/action though beta 2 integrin in vivo. J Leukoc Biol1996;59:145–51.
52.
LugowskiC. Immunotherapy in Gram-negative bacterial infections. Acta Biochim Pol1995;42:19–24.
53.
BoneRC. Gram-positive organisms and sepsis. Arch Intern Med1994;154:26–34.
54.
SawhneyRS, BoneRC. Endotoxin alters the expression of extracellular matrix proteins by cultured indothelial cells. Cell Mol Biol Res1993;39:589–99.
55.
SchumerW. Treatment of septic shock with steroids. In: HardawayR, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 475–80.
56.
ShatneyCH. The role of corticosteroids in the treatment of shock. In: HardawayRM, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 481–94.
57.
MacConnelKL. Vasoactive drugs in the treatment of shock. In: HardawayRM, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 495–505.
58.
BowenJC, ReesM. Endogenous opiates in shock. In: HardawayRM, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 505–11.
59.
GaffinSL. Antibody therapy in shock. In: HardawayRM, ed. Shock: The Reversible Stage of Dying. St. Louis, MO: Year Book Publishers, 1988, pp 511–6.
60.
DudleyMN. Interleukin-1 receptor antagonists significantly reduce death from sepsis: University of Rhode Island Multi-Center Study. Gen Surg News1993;28:28.
61.
Editor's Note. Gen Surg News1993;28:28.
62.
WegJG, BalkRA, TharrattRS, . Safety and potential efficiency of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome. JAMA1994;272:1433–8.
63.
QuezadoZMN, NatansonC, AilingDW, . A controlled trial of HA-IA in a canine model of Gram-negative septic shock. JAMA1993;269:2221–7.
64.
SingerSN, NicolsonGL. The fluid mosaic model of the structure of cell membranes: Cell membranes are viewed at two-dimensional solutions of oriented globular proteins and lipids. Science1973;175:720–31.
65.
SchwartzRS, ChiuDT-Y, LubinB. Studies on the organization of plasma membrane phospholipids in human erythrocyte. In: KrucheberWE, EatonJW, AsterJ, , eds. Erythrocyte Membranes 3: Recent Clinical and Experimental Advances. New York: AR Liss, 1984, pp 89–122.
66.
ChiuD, LubinB, ShohetSB. Erythrocyte membrane lipid reorganization during the sickling process. Br J Haematol1979; 41:223–34.
TuomanenE. Breaching the blood-brain barrier. Sci Am1996;268:80–4.
69.
HardawayRMIII, McKayDG. Disseminated intravascular coagulation: a cause of shock. Ann Surg1959;149:462–70.
70.
HardawayRM, HusniEA, GeeverEF, . Endotoxin shock: A manifestation of intravascular coagulation. Ann Surg1961;154:791–802.
71.
LandoisB. Die Transfusions Des Bluts.Lypzig1875.
72.
SchneiderCL. “Fibrin embolism” (disseminated intravascular coagulation) with defibrination as one of the end results during placenta abrupto. Surg Gynecol Obstet1951;92:27–34.
73.
HardawayRMIII, McKayD, WilliamsJH. Lower nephron nephrosis (ischemuric nephrosis) with special reference to hemorrhagic diathesis following incompatible blood transfusion reaction. Am J Surg1954;87:41–9.
74.
HardawayRM, McKayDG. Production of lower nephron nephrosis in dogs by means of an episode of intravascular clotting. Surg Forum1959;IX:1347.
75.
HardawayRM, McKayDG. Intravascular thrombi and the intestinal factor of irriversible shock. Ann Surg1959;150:261–5.
76.
HardawayRMIII, McKayDG, WahleGHJr, . Pathologic study of intravascular coagulation following incompatible blood transfusion in dogs. I. Intravenous injection of incompatible blood. Am J Surg1956;91:24–40.
77.
HardawayRM, McKayDG. Production of acute hemorrhagic pancreatitis in dogs by means of an episode of intravascular clotting in the pancreas. Surgery1959;45:557–61.
78.
HardawayRM, JohnsonD. A unified theory of shock. Am Surg1963;29:292–8.
HardawayRM. Syndromes of Disseminated Intravascular Coagulation with Speical Reference to Shock and Hemorrhage. Springfield, IL: Charles Thomas, 1966, p 5.
81.
HardawayRM, JamesPMJr, AndersonRW, . Intensive study and treatment of shock in man. JAMA1967;199:779–90.
82.
HardawayRM, HusniEA, GreeverEP, . Endotoxin shock: A manifestation intravascular coagulation. Ann Surg1961; 154:791–802.
83.
HardawayRM, JohnsonDG, ElovitzMJ, . Influence of trauma and hemolysis on hemorrhagic shock in dogs. J Trauma1964;4:624–41.
84.
HardawayRMIII. Mechanism of traumatic shock. Surg Gynecol Obstet1980;151:65–9.
85.
HardawayRM, BurnsJW. Mechanism of action of fibrinolysin in the presentation of “irreversible” hemorrhage shock. Ann Surg1963;157:305–9.
86.
HardawayRM, WilliamsCH. Prevention of multiple organ failure with plasminogen activator. Curr Ther Res1991;47: 711–22.
87.
HardawayRM, WilliamsCH, SunY. A new approach to the treatment of experimental septic shock. J Surg Res1996;61: 311–16.
88.
HardawayRM, Harke, WilliamsCH. Fibrinolytic agents: A new approach to the treatment of adult respiratory distress syndrome. Adv Ther1994;11:43–51.
89.
HardawayRM. Treatment of adult respiratory distress syndrome. Drugs Today1994;30:645–53.
HardawayRM, JohnsonDG, HouchinDN, . Influence of stress on fibrinogen. J Trauma1964;4:676–6.
92.
HardawayRM, DrakeDC. Prevention of “irreversible” hemorrhagic shock with fibrinolysin. Ann Surg1963;157:39–47.
93.
HardawayRM, JohnsonDG. Influence of fibrinolysin on shock. JAMA1963;183:597–9.
94.
HardawayRM, WilliamsCH, MarvastiM, . Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med1990;18:1413–8.
95.
HardawayRM. Trauma, sepsis, and disseminated intravascular coagulation. J Intensive Care Med1995;10:145–52.
96.
BoneRC. Reflecting and regrouping after failed trials: Sepsis researchers forge on. JAMA1996;275:823–4.
Shaw WarrenH. Strategies for the treatment of sepsis. N Engl J Med1997;336:952–3.
99.
BaueAE. Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome: Why no magic bullets?Arch Surg1997;132:703–7.
100.
OpalSM, FisherCJJr, DhainautJF, . Confirmatory interleukin-1 receptor antagonis trial in severe sepsis: A phase III, randomized double-blind, placebo-controlled, multicenter trial. Crit Care Med1997;25:1115–24.
101.
ZeniF, FreemanB, NatansonC. Anti-inflammatory therapies to treat sepsis and septic shock: A reassessment (Editorial). Crit Care Med1997;25:1095–100.
102.
AbrahamE, AnzuetoA, GutierrezG, . Double-blind randomized controlled trial fo monoclonal antibody to human tumor necrosis factor in treatment of septic shock. Lancet1998;351: 929–33.
103.
van DisselJT, van LangeveldeP, WestendorpRGJ, . Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet1998;351:950–3.
104.
VincentJ-L. Search for effective immunomodulating strategies against sepsis. Lance1998;351:922–3.
105.
AiutoLT, BaroneSR, CohenPS, BoxerRA. Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans. Crit Care Med1997;25:1079–82.
106.
HorneMK. Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans (Editorial). Crit Care Med1997;25:909.
107.
AdamsWH. Problems in Critical Care, Vol 3, No 1. Philadelphia: JB Lippincott, 1989, pp 108–38.
