NEW DEVELOPMENTS IN THE PATHOGENESIS AND TREATMENT OF SEPSIS

Authors

  • Matjaž Jereb Klinika za infekcijske bolezni in vročinska stanja Klinični center Japljeva 2 1525 Ljubljana
  • Andrej Trampuž Division of Infectious Diseases Department of Internal Medicine Mayo Clinic Rochester Minnesota USA

DOI:

https://doi.org/10.6016/ZdravVestn.1891

Keywords:

sepsis, pathogenesis, treatment

Abstract

Background. Severe sepsis and septic shock are the most important causes of death in patients in intensive care units. In the last decades the incidence of sepsis increased and the case-fatality rate of septic shock did not decreased significantly despite improved intensive care medicine. Clinical presentations of severe sepsis and septic shock are predominantly a result of dysregulation of the immune system caused by parts of the bacterial cell wall, endotoxins and exotoxins. Inflammatory cascade and cytokines plays an important role in the pathogenesis of sepsis.

Conclusions. Early and appropriate antimicrobial treatment as well as surgical removal of an septic focus improve the survival of patients with sepsis. In the past, various immunomodulatory therapies (antiendotoxins, antimediator interventions and immunostimulation therapy) did not decreased the mortality of patients with sepsis. In the last years, however, some interventions in selected patients with severe sepsis and septic shock have shown significantly improved survival. These interventions include treatment with activated protein C, early goal-directed therapy, intensive treatment with insulin, low-dose corticosteroid treatment and use of low tidal volumes in patients with acute lung injury or acute respiratory distress syndrome. In this article new developments in pathogenesis and therapy of sepsis are reviewed.

Downloads

Download data is not yet available.

References

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303–10.

Bone RC, Balk RA, Cerra FB et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/ Society of Critical Care Medicine. Chest 1992; 101: 1644–55.

Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 1995; 273: 117–23.

Anon. Acute myocardial infarction: pre-hospital and in-hospital management. The task force on the management of acute myocardial infarction of the European Society of Cardiology. Eur Heart J 1996; 17: 43–63.

Vincent JL. Dear SIRS, I’m sorry to say that I don’t like you… Crit Care Med 1997; 25: 372–4.

Marshall JC. SIRS and MODS: what is their relevance to the science and practice of intensive care? Shock 2000; 14: 586–9.

Abraham E, Matthay MA, Dinarello CA et al. Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation. Crit Care Med 2000; 28: 232–5.

Levy MM, Fink MP, Marshall JC et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 31: 1250–6.

Bossink AW, Groeneveld AB, Thijs LG. Prediction of microbial infection and mortality in medical patients with fever: plasma procalcitonin, neutrophilic elastase-alpha1-antitrypsin, and lactoferrin compared with clinical variables. Clin Infect Dis 1999; 29: 398–407.

Harbarth S, Holeckova K, Froidevaux C et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001; 164: 396–402.

Landmann R, Zimmerli W, Sansano S et al. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock. J Infect Dis 1995; 171: 639–44.

Fassbender K, Pargger H, Muller W, Zimmerli W. Interleukin-6 and acutephase protein concentrations in surgical intensive care unit patients: diagnostic signs in nosocomial infection. Crit Care Med 1993; 21: 1175–80.

Muller B, Becker KL, Schachinger H et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000; 28: 977–83.

Landmann R, Reber AM, Sansano S, Zimmerli W. Function of soluble CD14 in serum from patients with septic shock. J Infect Dis 1996; 173: 661–8.

Bochud PY, Calandra T. Pathogenesis of sepsis: new concepts and implications for future treatment. BMJ 2003; 326: 262–6.

Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 2000; 181: 176–80.

Calandra T, Bochud PY, Heumann D. Cytokines in septic shock. Curr Clin Top Infect Dis 2002; 22: 1–23.

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348: 138–50.

Hebert PC, Drummond AJ, Singer J, Bernard GR, Russell JA. A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome. Chest 1993; 104: 230–5.

Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999; 340: 207–14.

Shenep JL, Mogan KA. Kinetics of endotoxin release during antibiotic therapy for experimental gram-negative bacterial sepsis. J Infect Dis 1984; 150: 380–8.

Pittet D, Thievent B, Wenzel RP, Li N, Auckenthaler R, Suter PM. Bedside prediction of mortality from bacteremic sepsis. A dynamic analysis of ICU patients. Am J Respir Crit Care Med 1996; 153: 684–93.

Fluckiger U, Zimmerli W, Sax H, Frei R, Widmer AF. Clinical impact of an infectious disease service on the management of bloodstream infection. Eur J Clin Microbiol Infect Dis 2000; 19: 493–500.

Zimmerli W. Sepsis. In: Gyr NE, Schoenenberger RA, Haefeli WE eds. Internistische Notfälle. Stuttgart-New York: Georg Thieme Verlag, 2001: 229–31.

Fisher CJ, Agosti JM, Opal SM et al. Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 1996; 334: 1697–702.

Vincent JL, Sun Q, Dubois MJ. Clinical trials of immunomodulatory therapies in severe sepsis and septic shock. Clin Infect Dis 2002; 34: 1084–93.

Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcome in severe sepsis. Chest 2001; 120: 915–22.

Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699– 709.

Cronin L, Cook DJ, Carlet J et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 1995; 23: 1430–9.

Annane D, Sebille V, Charpentier C et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862–71.

Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368–77.

Van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 1359–67.

Martin GS, Bernard GR. Airway and lung in sepsis. Intensive Care Med 2001; 27: Suppl 1: S63–S79.

Anon. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342: 1301–8.

Baumgartner JD, Glauser MP, McCutchan JA et al. Prevention of gramnegative shock and death in surgical patients by antibody to endotoxin core glycolipid. Lancet 1985; 2: 59–63.

Bone RC, Balk RA, Fein AM et al. A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. Crit Care Med 1995; 23: 994–1006.

Levin M, Quint PA, Goldstein B et al. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 2000; 356: 961–7.

Abraham E, Anzueto A, Gutierrez G et al. Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 1998; 351: 929–33.

Abraham E, Laterre PF, Garbino J et al. Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients. Crit Care Med 2001; 29: 503–10.

Reinhart K, Menges T, Gardlund B et al. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study. Crit Care Med 2001; 29: 765–9.

Opal SM, Fisher CJ, Dhainaut JF et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med 1997; 25: 1115–24.

Fisher CJ Jr, Dhainaut JF, Opal SM et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 1994; 271: 1836–43.

Remick DG, Call DR, Ebong SJ et al. Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sepsis mortality. Crit Care Med 2001; 29: 473–81.

Preiser JC, Lejeune P, Roman A et al. Methylene blue administration in septic shock: a clinical trial. Crit Care Med 1995; 23: 259–64.

Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res 1994; 28: 34–9.

Avontuur JA, Tutein-Nolthenius RP, van Bodegom JW, Bruining HA. Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study. Crit Care Med 1998; 26: 660–7.

Bernard GR, Wheeler AP, Russell JA et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 1997; 336: 912–8.

Fourrier F, Chopin C, Huart JJ, Runge I, Caron C, Goudemand J. Doubleblind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 1993; 104: 882–8.

Warren BL, Eid A, Singer P et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286: 1869–78.

Dhainaut JF, Tenaillon A, Hemmer M et al. Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group. Crit Care Med 1998; 26: 1963–71.

Dhainaut JF, Tenaillon A, Le Tulzo Y et al. Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group. Crit Care Med 1994; 22: 1720–8.

Vincent JL, Spapen H, Bakker J, Webster NR, Curtis L. Phase II multicenter clinical study of the platelet-activating factor receptor antagonist BB-882 in the treatment of sepsis. Crit Care Med 2000; 28: 638–42.

Spies CD, Reinhart K, Witt I et al. Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study. Crit Care Med 1994; 22: 1738–46.

Angstwurm MW, Schottdorf J, Schopohl J, Gaertner R. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Crit Care Med 1999; 27: 1807–13.

Wunderink R, Leeper K Jr, Schein R et al. Filgrastim in patients with pneumonia and severe sepsis or septic shock. Chest 2001; 119: 523–9.

Arslan E, Yavuz M, Dalay C. The relationship between tumor necrosis factor (TNF)-alpha and survival following granulocyte-colony stimulating factor (G-CSF) administration in burn sepsis. Burns 2000; 26: 521–4.

Root RK, Lodato RF, Patrick W et al. Multicenter, double-blind, placebocontrolled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis. Crit Care Med 2003; 31: 367–73.

Wasserman D, Ioannovich JD, Hinzmann RD, Deichsel G, Steinmann GG. Interferon-gamma in the prevention of severe burn-related infections: a European phase III multicenter trial. The Severe Burns Study Group. Crit Care Med 1998; 26: 434–9.

How to Cite

1.
NEW DEVELOPMENTS IN THE PATHOGENESIS AND TREATMENT OF SEPSIS. ZdravVestn [Internet]. 2003 Dec. 7 [cited 2024 Nov. 2];72(12). Available from: https://vestnik.szd.si/index.php/ZdravVest/article/view/1891

Most read articles by the same author(s)

1 2 > >>