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Pathophysiology and Therapy of End-Organ Failure in Critical Illness

  • M. R. Pinsky

Abstract

The pattern of death of critically ill patients aggressively treated with lifesustaining therapies following the initial resuscitative effort is remarkably similar across patient groups (1). Most of the critically ill patients who eventually go on to die during that hospitalization in whom initial resuscitative efforts are successful do so because of progressive multi-system deterioration often punctuated by infectious episodes and a non-specific septic state. The clinical expression of this initial process a sepsis or sepsis syndrome has been termed the systemic inflammatory response syndrome or SIRS by a recent consensus conference (2). The deterioration of these patients over time with progressive failure of multiple often unrelated organ systems is referred to a multiple organ dysfunction syndrome or MODS to underscore the continuum of tissue injury which may develop rather than by defining a threshold level to indicate the presence of organ failure. Patients usually first express SIRS and then MODS, progressing along a clinical pathway from initial partial recovery following resuscitation, though relapses and septic episodes to death. Diverse disease states such as infection, trauma and burns, pancreatitis and organ rejection share this common process (1). It is our hypothesis that MODS represents the phenomenological process of progressive and cumulative organ system dysfunction that may occur after a variety of diseases characterized by continual intravascular inflammation (3). According to this hypothesis, specific organ dysfunction is less important to outcome than the cumulative tissue burden of SIRS.

Keywords

Septic Shock Acute Lung Injury Critical Illness Adult Respiratory Distress Syndrome Immune Effector Cell 
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.

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References

  1. 1.
    Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple-Organ-Failure Syndrome. Arch Surg 121:196–200PubMedCrossRefGoogle Scholar
  2. 2.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874CrossRefGoogle Scholar
  3. 3.
    Pinsky MR, Matuschak GM (1990) Multiple systems organ failure: a unifying hypothesis. J Crit Care 5:108–114CrossRefGoogle Scholar
  4. 4.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) Prognosis in acute organ-system failure. Ann Surg 202:685–693PubMedCrossRefGoogle Scholar
  5. 5.
    Montgomery AB, Stager MA, Carrico CJ, Hudson LD (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Resp Dis 132:485–489PubMedGoogle Scholar
  6. 6.
    Butkus DE (1983) Persistent high mortality in acute renal failure. Arch Intern Med 143: 209–212PubMedCrossRefGoogle Scholar
  7. 7.
    Pinsky MR (1989) Multiple systems organ failure: Malignant intravascular inflammation. In: Pinsky MR and Matuschak GM (eds.) Multiple systems organ failure. Chn Crit Care 5(2): 195–198Google Scholar
  8. 8.
    Movat HZ, Cybulsky MI, Colditz IG, Chan MK, Dinarillo CA (1987) Acute inflammation in Gram-negative infection: endotoxin, interleukin-1, tumor necrosis factor, and neutrophils. Fed Proc 46:97–104PubMedGoogle Scholar
  9. 9.
    Korthuis RJ, Anderson DC, Granger DN (1994) Role of neutrophil-endothelial cell adhesion in inflammatory disorders. J Crit Care 9:47–71PubMedCrossRefGoogle Scholar
  10. 10.
    Tracy KJ, Beutler B, Lowery SF et al (1986) Shock and tissue injury induced by recombinant human cachectin. Science 234:470–474CrossRefGoogle Scholar
  11. 11.
    Dinarello CA, Cannon JG, Wolff SM et al (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin-1. J Exp Med 163:1433–1450PubMedCrossRefGoogle Scholar
  12. 12.
    Cybulsky MI, Colditz IG, Movat HZ (1986) The role of interieukin-1 in neutrophil leukocyte migration induced by endotoxin. Am J Pathol 124:367–372PubMedGoogle Scholar
  13. 13.
    Tracy KJ, Cerami A (1993) Tumor necrosis factor: an updated review of its biology. Crit Care Med 21:S415-S422Google Scholar
  14. 14.
    Michie HR, Manogue KR, Spriggs DR, Revhaug A, O’Dwyer S, Dinarello CA et al (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318:1481–1486PubMedCrossRefGoogle Scholar
  15. 15.
    Beutler B, Milsark IW, Cerami A (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871PubMedCrossRefGoogle Scholar
  16. 16.
    Waage A, Brandtzaeg P, Halsteusen A, Kierulf P, Espevik T (1989) The complex pattern of cytokines in the serum of patients with meningococcal septic shock. J Exp Med 169:333–338PubMedCrossRefGoogle Scholar
  17. 17.
    Waage A, Halstensen A, Espevik T (1987) Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1:355–357PubMedCrossRefGoogle Scholar
  18. 18.
    Hack CE, DeGroot ER, Felt-Bersma RJF, Nuijens JH, Strack van Schijundel RS, Eerenberg- Belmer AJ et al (1989) Increased plasma levels of interleukin-6 in sepsis. Blood 74:1704–1710PubMedGoogle Scholar
  19. 19.
    Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn R, Dupont E (1993) Serum cytokine levels in human septic shock: Relation to multiple systems organ failure and mortality. Chest 103:565–575PubMedCrossRefGoogle Scholar
  20. 20.
    Wright SD, Ramos RA, Tobias PS et al (1990) CD 14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249:1431–1433PubMedCrossRefGoogle Scholar
  21. 21.
    Chouaib S, Welte K, Mertelsmann R, DuPont B (1985) Prostaglandin E, acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down regulation of transferrin receptor expression. J Immunol 135:1172–1179PubMedGoogle Scholar
  22. 22.
    Beutler B, Tkacenko V, Milsark I et al (1986) Effect of gamma interferon on cachectin expression by mononuclear phagocytes. J Exp Med 164:1791–1796PubMedCrossRefGoogle Scholar
  23. 23.
    Stotman GJ, Burchard KW, Williams JJ, D’Anezzo A, Yellin SA (1986) Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension. Surgery 99:744–751Google Scholar
  24. 24.
    Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxation factor. Nature 327:524–526PubMedCrossRefGoogle Scholar
  25. 25.
    Altura BM, Gegrewold A, Burton RW (1985) Failure of microscopic metarterioles to elicit vasodilator responses to acetylcholine, bradykinin, histamine, and substance P after ischemic shock, endotoxemia, and trauma: possible role of endothelial cells. Microcirc Endothelium Lymphatics 2:121–129PubMedGoogle Scholar
  26. 26.
    Buckley G (1983) The role of oxygen free radicals in human disease processes. Surgery 94: 407–414Google Scholar
  27. 27.
    Morgan RA, Manning PB, Coran AG et al (1988) Oxygen free radical activity during live E. coh septic shock in the dog. Circ Shock 25:319–323PubMedGoogle Scholar
  28. 28.
    Matuschak GM, Rinaldo JE (1988) Organ interactions in the adult respiratory distress syndrome during sepsis. Role of the liver in host defense. Chest 94:400–406PubMedCrossRefGoogle Scholar
  29. 29.
    Weksler BB, Goldstein IM (1980) Prostaglandins: interactions with platelets and polymorphonuclear leukocytes in hemostasis and inflammation. Am J Med 68:419–428PubMedCrossRefGoogle Scholar
  30. 30.
    Ziegler EJ, McCutchan JA, Fierer J et al (1982) Treatment of Gram-negative bacteremia and shock with human antiserum to a mutant E. coh. N Engl J Med 307:1225–1230CrossRefGoogle Scholar
  31. 31.
    Ziegler EJ and the HA-1A Sepsis Study Group (1991) Treatment of gram negative bacteremia and septic shock with HA-IA human monoclonal antibody against endotoxin: a randomized, double-bhnd, placebo-controlled trial. N Engl J Med 324:429–436PubMedCrossRefGoogle Scholar
  32. 32.
    Greenman RL, Schein RMH, Martin MA et al (1991) A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA 266: 1097–1102PubMedCrossRefGoogle Scholar
  33. 33.
    McCloskey RV, Straube RC, Sanders C, Smith SM, Smith CR and the CHESS Trail Study Group (1994) Treatment of septic shock with human monoclonal antibody HA-IA: A randomized, double-blind, placebo-controlled trial. Ann Intern Med 121:1–5PubMedGoogle Scholar
  34. 34.
    Hinchaw LB, Beller BK, Chang ACK et al (1986) Effect of prior administration of steroids upon recovery from lethal sepsis. Surg Gynecol Obstet 163:335–344Google Scholar
  35. 35.
    Lefer AM, Tabas J, Smith EF (1980) Salutory effects of prostacyclin in endotoxic shock. Pharmacology 21:206–212PubMedCrossRefGoogle Scholar
  36. 36.
    Sprung CL, Caralis PV, Marciai EH et al (1984) The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med 311:1137–1143PubMedCrossRefGoogle Scholar
  37. 37.
    Bone RC, Fisher CJ, Clemmer TP et al (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317: 653–659PubMedCrossRefGoogle Scholar
  38. 38.
    Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL et al (1994) Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. JAMA 271:1836–1843PubMedCrossRefGoogle Scholar
  39. 39.
    Abraham E, Wunderink R, Silverman H, Peri TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Alfred R, Pennington JE, Wherry JC et al (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor a in patients with sepsis syndrome. JAMA 273: 934–941PubMedCrossRefGoogle Scholar
  40. 40.
    Luce JM (1993) Introduction to new technology into critical care practice: a history of HA-1A human monoclonal antibody against endotoxin. Crit Care Med 21:1233–1241PubMedCrossRefGoogle Scholar
  41. 41.
    Gnidec AC, Sibbald WJ, Cheung H, Metz CA (1988) Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis. J Appi Physiol 65:1024–1032Google Scholar
  42. 42.
    Fink MP, Morrissey PE, Stein KL et al (1988) Systemic and regional hemodynamic effects of cyclo-oxygenase and thromboxane synthetase inhibition in normal and hyperdynamic endotoxic rabbits. Circ Shock 26:41–57PubMedGoogle Scholar
  43. 43.
    Kilboum RO, Gross SS, Jubran A et al (1990) N-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 87:3629–3632CrossRefGoogle Scholar
  44. 44.
    Bell R, Coalson J, Smith J et al (1983) Multiple organ system failure and infection and the adult respiratory distress syndrome. Ann Intern Med 99:293–298PubMedGoogle Scholar
  45. 45.
    Fry D, Pearlstein L, Fulton R et al (1980) Multiple system organ failure. The role of uncontrolled infection. Arch Surg 115:136–140PubMedCrossRefGoogle Scholar
  46. 46.
    Gutierrez G, Palizas F, Doglio G et al (1992) Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet 339:195–199PubMedCrossRefGoogle Scholar
  47. 47.
    Matuschak GM, Rinaldo JE, Pinsky MR, Gavaler JS, Van Thiel DH (1987) Effect of end-stage liver failure on the incidence and resolution of the adult respiratory distress syndrome. J Crit Care 2:162–173CrossRefGoogle Scholar
  48. 48.
    Lamy M, Fallat RJ, Koeniger E et al (1976) Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114:267–284PubMedGoogle Scholar
  49. 49.
    Gattinoni L, Persemi A, Avalli L, Rossi F, Bombino M (1987) Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis 136:730–736PubMedCrossRefGoogle Scholar
  50. 50.
    Dreyfuss D, Bassett G, Soler P, Saumon G (1985) Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis 132:880–884PubMedGoogle Scholar
  51. 51.
    Deitch EA, Winterton J, Bey R (1987) The gut as the portal of entry for bacteremia. Ann Surg 205:681–692PubMedCrossRefGoogle Scholar
  52. 52.
    Ledingham IMcA, Allcock SR, Eastaway AT et al (1988) Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. Lancet 1:785–790PubMedCrossRefGoogle Scholar
  53. 53.
    Pinsky MR (1990) Hemodynamic Effects of Mechanical Ventilation. Appi Cardiopulm Pathophysiol 3:219–227Google Scholar
  54. 54.
    Valenza F, Ribeiro SP, Slutsky AS (1995) High volume low pressure mechanical ventilation up-regulates IL-Iß production in an ex vivo lung model, [abstract] Am J Respir Crit Care Med 151:A552Google Scholar
  55. 55.
    Bergstrom J (1978) Ultrafiltration without dialysis for removal of fluid and solutes in uremia. Clin Nephrol 9:156–164PubMedGoogle Scholar
  56. 56.
    Pugin J, Auckenthaler R, Lew DP, Suter PM (1991) Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA 265:2704–2710PubMedCrossRefGoogle Scholar
  57. 57.
    Hickling KG, Walsh J, Henderson S et al (1994) Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: A prospective study. Crit Care Med 22:1568–1578PubMedCrossRefGoogle Scholar
  58. 58.
    Ossenkoppele GJ, van der Meulen J, Bronsveld W, Thijs LG (1985) Continuous arteriovenous hemofiltration as an adjuctive therapy for septic shock. Crit Care Med 13:102–104PubMedCrossRefGoogle Scholar
  59. 59.
    Kaplan AA, Longnecker RE, Folkert VW (1984) Continuous arteriovenous hemofiltration: a report on six months’ experience. Ann Intern Med 100:358–367PubMedGoogle Scholar
  60. 60.
    Reidy JJ, Ramsay G (1990) Clinical trials of selective decontamination of the digestive tract: review. Crit Care Med 18:1449–1456PubMedCrossRefGoogle Scholar
  61. 61.
    Blanch L, Fernandez R, Valle J, Sole J, Roussos Ch, Artegas A (1994) Effect of two tidal volumes on oxygenation and respiratory system mechanics during the early stage of adult respiratory distress syndrome. J Crit Care 9:151–158PubMedCrossRefGoogle Scholar
  62. 62.
    Grootendorst AF, Van Bommel EF, Van Leengoed LA et al (1994) High volume hemofiltration improves hemodynamics and survival in pigs exposed to gut ischemia and reperfusion. Shock 2:72–78PubMedCrossRefGoogle Scholar
  63. 63.
    Grootendorst AF, Van Bommel EF, Van Leengoed LA et al (1993) Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs. J Care Med 8: 161–169Google Scholar
  64. 64.
    Vincent J-L, Tielemans C (1995) Continuous hemofiltration in severe sepsis: is it beneficial? J Crit Care 10:27–32PubMedCrossRefGoogle Scholar
  65. 65.
    Smith SD, Jackson RJ, Hannakan CJ et al (1993) Selective decontamination in pediatric liver transplants. A randomized prospective study. Transplantafion 55:1306–1309CrossRefGoogle Scholar
  66. 66.
    Tetteroo GW, Wagenvoort JH, Mulder PG, Ince C, Bruining HA (1993) Decreased mortality rate and length of stay in surgical intensive care pafients with successful decontaminafion of the gut. Crit Care Med 21:1692–1698PubMedCrossRefGoogle Scholar

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© Springer-Verlag Italia, Milano 1996

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  • M. R. Pinsky

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