Pneumologie 2009; 63(4): 197-204
DOI: 10.1055/s-0028-1119702
Serie: Intensiv- und Beatmungsmedizin

© Georg Thieme Verlag KG Stuttgart · New York

Die Therapie der schweren Sepsis

Treatment of Severe SepsisJ.  Lorenz1
  • 1Klinik für Pneumologie, Internistische Intensivmedizin, Infektiologie und Schlafmedizin, Klinikum Lüdenscheid
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
16. März 2009 (online)

Zusammenfassung

Als Sepsis wird eine Infektion mit systemischer Manifestation bezeichnet. Bei Vorliegen mindestens eines Organversagens handelt es sich um eine schwere Sepsis. Die Bedeutung des Krankheitsbildes in der Pneumologie ergibt sich aus der Tatsache, dass in der nichtoperativen Medizin die Pneumonie die häufigste Sepsisursache und das akute Lungenversagen eine der Hauptmanifestationen der schweren Sepsis darstellen. Die empirische Basis der Sepsisbehandlung ist einem erheblichen Wandel unterworfen, da im letzten Jahrzehnt erstmals durch die Bildung von Studiengruppen und Kompetenzzentren die Durchführung großer, aussagekräftiger Interventionsstudien ermöglicht wurde. Neben der Kontrolle der zugrunde liegenden Infektion umfasst die Therapie der schweren Sepsis die Behandlung hämodynamischer, respiratorischer, endokrinologischer, koagulatorischer und immunologischer Aspekte der Erkrankung. Während die neuen Konzepte der Schockbehandlung und der Beatmungstherapie bestätigt werden konnten, sind Ansätze der Antikoagulation und die endokrinologische und die immunologische Therapie noch im Fluss.

Abstract

The sepsis syndrome is defined as a clinically suspected infection accompanied by systemic manifestations. The emergence of one or multiple organ dysfunctions is the hallmark of severe sepsis. The significance of sepsis in pulmonary medicine is highlighted by the fact that severe pneumonia is the most prevalent cause of sepsis in non-surgical intensive care medicine and that acute lung injury is among the prominent manifestations of severe sepsis. The formation of major study groups and competence centres during the last decade has made meaningful prospective interventional studies possible that, in turn, have resulted in the development of clinical treatment algorithms. Today, the multidisciplinary treatment of severe sepsis includes haemodynamic, respiratory, endocrine, immune, and coagulation aspects besides the control of the underlying infection. While new concepts of shock treatment and mechanical ventilation have been established by means of confirmatory studies, endocrine interventions as well as immune and anticoagulation procedures are still under investigation.

Literatur

  • 1 Bone R C, Balk R A, Cerra F B. et al . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee.  Chest. 1992;  101 1644-1655
  • 2 Vincent J L. Dear SIRS, I'm sorry to say that I don't like you.  Crit Care Med. 1997;  25 372-374
  • 3 Alberti C, Brun-Buisson C, Chevret S. et al . Systemic inflammatory response and progression to severe sepsis in critically ill infected patients.  Am J Respir Crit Care. 2005;  171 461-468
  • 4 Wheeler A P, Bernard G R. Treating patients with severe sepsis.  N Engl J Med. 1999;  340 207-214
  • 5 Annane D, Bellisant E, Cavaillon J M. Septic shock.  Lancet. 2005;  365 63-78
  • 6 Sands K E, Bates D W, Lanken P N. et al . Epidemiology of sepsis syndrome in 8 academic medical centers.  JAMA. 1997;  278 234-240
  • 7 Angus D, Linde-Zwirble W T, Lidicker J. et al . Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated cost of care.  Crit Care Med. 2001;  29 1303-1310
  • 8 Annane D, Aegerter P, Jars-Guincestre M C. et al . Current epidemiology of septic shock.  Am J Respir Crit Care Med. 2003;  168 165-172
  • 9 Brunkhorst F M, Engel C, Welte T. et al . Prevalence of infection in German Intensive Care Units – Results from the German Prevalence Study.  Infection. 2005;  33 (Suppl 1) 47
  • 10 Marini J J, Wheeler A P. Severe Sepsis. In: Marini JJ, Wheeler AP (eds). Critical Care Medicine – The Essentials, 3rd Edition. Philadelphia; Lippincott, Williams and Wilkins 1997: 451-465
  • 11 Wurfel M M, Gordon A C, Holden T D. et al . Toll-like receptor 1 polymorphisms affect innate immune responses and outcome in sepsis.  Am J Respit Crit Care Med. 2008;  178 710-720
  • 12 Christ-Crain M, Stolz D, Bingisser R. Effect of procalcitonin-guided therapy in community-acquired pneumonia: a randomized trial.  Am J Respir Crit Care Med. 2006;  174 84-93
  • 13 Harbarth S, Holeckova K, Froidevaux C. 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
  • 14 Nobre V, Harbarth S, Graf J D. et al . Use of procalcitonin to shorten antibiotic treatment duration in septic patients.  Am J Respir Crit Care Med. 2008;  177 498-505
  • 15 Brunkhorst F M, Engel C, Jaschinsky U. et al . Treatment of severe sepsis and septic shock in Germany – the gap between perception and practice. Results from the German prevalence study.  Intensivmed.up2date. 2006;  2 89-90
  • 16 Intravenous Immunoglobulin Collaborative Study Group . Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection.  N Engl J Med. 1992;  327 234-240
  • 17 Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group.  Crit Care Med. 1996;  24 1431-1440
  • 18 Panacek E A, Marshall J, Fischkoff S. et al . Neutralization of TNF by a monoclonal antibody improves survival and reduces organ dysfunction in human sepsis: results of the MONARCS trial.  Chest. 2000;  118 (Suppl) 88
  • 19 Abraham E, Reinhart K, Opal S, Demeyer I, Doig C. for the OPTIMIST Trial Study Group . Efficacy and safety of Tifacogin (recombinant tissue factor) in severe sepsis.  JAMA. 2003;  290 238-247
  • 20 Angstwurm M WA, Engelmann L, Zimmermann T. et al . Selenium in intensive care (SIC): Results of a prospective randomized, placebo-controlled, multiple center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.  Crit Care Med. 2007;  325 118-126
  • 21 Kumar A, Roberts D, Wood K E. et al . Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.  Crit Care Med. 2006;  34 1589-1595
  • 22 Garey K W, Rege M, Pai M P. et al . Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: A multi-institutional study.  Clin Infect Dis. 2006;  43 25-31
  • 23 McGarvey R N, Harper J J. Pneumonia mortality reduction and quality improvement in a community hospital.  QRB Qual Rev Bull. 1993;  19 124-130
  • 24 Meehan T P, Fine M J, Krumholz H M. Quality of care, process, and outcomes in elderly patients with pneumonia.  JAMA. 1997;  278 2080-2084
  • 25 Iregui M, Ward S, Sherman G. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia.  Chest. 2002;  122 262-268
  • 26 Gacouin A, Le Tulco Y, Lavoue S. Severe pneumonia due to Legionella pneumophila: Prognostic factors, impact of delayed appropriate antimicrobial therapy.  Intensive Care Med. 2002;  28 686-691
  • 27 Proulx N, Frechette D, Toye B. Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis.  QJM. 2005;  98 291-298
  • 28 Kang C I, Kim S H, Kim H B. Pseudomonas aeruginosa bacteremia: Risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome.  Clin Infect Dis. 2003;  37 745-751
  • 29 Lodise T P, McKinnon P S, Swiderski L. Outcome analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia.  Clin Infect Dis. 2003;  36 1418-1423
  • 30 Höffken G, Lorenz J, Kern W V. et al . S3-Leitlinie der Paul-Ehrlich-Gesellschaft für Chemotherapie, der Deutschen Gesellschaft für Pneumologie, der Deutschen Gesellschaft für Infektiologie und des Kompetenznetzwerkes CAPNETZ zu Epidemiologie, Diagnostik, antimikrobieller Therapie und Management von erwachsenen Patienten mit ambulant erworbenen tiefen Atemwegsinfektionen (akute Bronchitis, akute Exazerbation einer chronischen Bronchitis, Influenza und andere respiratorische Virusinfektionen) sowie ambulant erworbener Pneumonie.  Pneumologie. 2005;  59 612-664
  • 31 Gleason P P, Meehan T P, Fine J M. et al . Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia.  Arch Intern Med. 1999;  159 2562-2572
  • 32 Houck P M, MacLehose R F, Niederman M S. et al . Empiric antibiotic therapy and mortality among medicare pneumonia inpatients in 10 western states: 1993, 1995, and 1997.  Chest. 2001;  119 1420-1426
  • 33 Martinez J A, Horcajada J P, Almela M. et al . Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia.  Clin Infect Dis. 2003;  36 389-395
  • 34 Mufson M A, Stanek R J. Bacteremic pneumococcal pneumonia in one American City: a 20-year longitudinal study, 1978 – 1997.  Am J Med. 1999;  107 34S-43S
  • 35 Stahl J E, Barza M, DesJardin J. et al . Effect of macrolides as part of initial empiric therapy on length of stay in patients hospitalized with community-acquired pneumonia.  Arch Intern Med. 1999;  159 2576-2580
  • 36 Baddour L M, Yu V L, Klugman K P. et al . Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia.  Am J Respir Crit Care Med. 2004;  170 440-444
  • 37 Chastre J, Wolff M, Fagon J Y. et al . Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.  JAMA. 2003;  290 2588-2598
  • 38 Rodriguez A, Mendia A, Sirvent J M. et al . Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock.  Crit Care Med. 2007;  35 1493-1498
  • 39 Rivers E, Nguyen B, Havstad S. Early goal directed therapy in the treatment of severe sepsis and septic shock.  N Engl J Med. 2001;  345 1368-1377
  • 40 Trzeciak S, Dellinger R P, Abate N L. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department.  Chest. 2006;  129 225-232
  • 41 Dellinger R P, Levy M M, Carlet J M. et al . Surviving Sepsis Campaign: International guidelines management of severe sepsis and septic shock: 2008.  Critical Care Med. 2008;  36 296-327
  • 42 Wilkes M M, Navickis R J. Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials.  Ann Intern Med. 2001;  135 149-164
  • 43 Hollenberg S M, Ahrens T S, Annane D. et al . Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update.  Crit Care Med. 2004;  32 1928-1948
  • 44 Brunkhorst F M, Engel C, Bloos F. et al . Intensive insulin therapy and pentastarch rescucitation in severe sepsis.  N Engl J Med. 2008;  358 125-139
  • 45 Russell J A, Walley K R, Singer J. et al . Vasopressin versus norepinephrin infusion in patients with septic shock.  N Engl J Med. 2008;  358 877-887
  • 46 Charles P E, Martin L, Etienne M. et al . Influence of positive end-expiratory pressure (PEEP) on histopathological and bacteriological aspects of pneumonia during low tidal volume mechanical ventilation.  Intensive Care Med. 2004;  30 2263-2270
  • 47 Sakr Y, Vincent J L, Reinhart K. et al . High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury.  Chest. 2005;  128 3098-3018
  • 48 Stüber F, Wrigge H, Schröder S. et al . Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury.  Intensive Care Med. 2002;  28 834-841
  • 49 Dreyfuss D, Saumon S. State of the art: Ventilator-induced lung injury.  Am J Respir Crit Care Med. 1998;  157 294-323
  • 50 Amato M B, Barbas C S, Medeiros D M. et al . Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.  N Engl J Med. 1997;  338 347-354
  • 51 The A cute. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.  N Engl J Med. 2000;  342 1301-1308
  • 52 Hager D N, Krishnan J A, Hayden D L. et al . Tidal volume reduction in patients with acute lung injury when plateau pressures are not high.  Am J Respir Crit Care Med. 2005;  172 1241-1245
  • 53 Hickling K G, Henderson S J, Jackson L. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome.  Intensive Care Med. 1990;  16 372-377
  • 54 Brower R G, Lanken P N, MacIntyre N. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.  N Engl J Med. 2004;  351 327-336
  • 55 Mercat A, Richard J M, Vielle B. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome (EXPRESS).  JAMA. 2008;  299 646-655
  • 56 Meade M O, Cook D J, Guyatt G H. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.  JAMA. 2008;  299 637-645
  • 57 Grasso S, Stripoli T, De Michele M. et al . ARDSnet Ventilatory Protocol and Alveolar Hyperinflation: Role of Positive End-Expiratory Pressure.  Am J Respir Crit Care Med. 2007;  176 761-767
  • 58 Lorenz J. Akuter Lungenschaden und akutes Atemnotsyndrom (ARDS). In: Weilemann S, Lorenz J, Voigtländer T (Hrsg). Internistische Intensivmedizin und Notfallmedizin. Heidelberg; Springer 2007: 249-260
  • 59 Rothwell P M, Udwadia Z F, Lawler P G. Cortisol response to corticotropin and survival in sepsis.  Lancet. 1991;  337 582-583
  • 60 Sprung C L, Annane D, Keh D. et al . Hydrocortisone therapy for patients with septic shock.  N Engl J Med. 2008;  358 111-124
  • 61 Annane D, Maxime V, Ibrahim F. et al . Diagnosis of adrenal insufficiency in severe sepsis and septic shock.  Am J Respir Crit Care Med. 2006;  174 1319-1326
  • 62 Annane D, Sébille V, Troché G. et al . A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin.  JAMA. 2000;  283 1038-1045
  • 63 Annane D, Sebille V, Charpentier C. et al . Effect of treatment with low doses of hydrocortisone and fludrocortisones on mortality in patients with septic shock.  JAMA. 2002;  288 862-871
  • 64 Van den Berghe G, Wouters P, Weekers F. Intensive insulin therapy in critically ill patients.  N Engl J Med. 2001;  345 1359-1367
  • 65 Van den Berghe G, Wilmer A, Hermans G. Intensive insulin therapy in the medical ICU.  N Engl J Med. 2006;  354 449-461
  • 66 Levi M, de Jonge E, van der Poll T. New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology.  Ann Med. 2004;  36 41-49
  • 67 Opal S M, Kessler C M, Roemisch J. et al . Antithrombin, heparin, and heparan sulfate.  Crit Care Med. 2002;  30 (5 suppl) 325-331
  • 68 Rublee D, Opal S M, Schramm W. et al . Quality of life effects of antithrombin III in sepsis survivors: results from the KyberSept trial.  Crit Care. 2002;  6 349-356
  • 69 Warren B L, Eid A, Singer P. et al . KyberSept Trial Study Group: High-dose antithrombin III in severe sepsis. A randomized controlled trial.  JAMA. 2001;  286 1869-1878
  • 70 Afshari A. Antithrombin III in critically ill patients: Systematic review with meta-analysis and trial sequential analysis.  BMJ. 2007;  335 248-1256
  • 71 Wiedermann C J, Hoffmann J N, Juers M. et al . High-dose antithrombin III in the treatment of severe sewpsis in patients with a high risk of death: Efficacy and safety.  Crit Care Med. 2006;  34 285-291
  • 72 Bernard G R, Vincent J L, Laterre P F. et al . For the recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) study group: efficacy and safety of recombinant human activated protein C for severe sepsis.  N Engl J Med. 2001;  344 699-709
  • 73 Dhainaut J F, Laterre P F, Janes J M. et al . Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ failure dysfunction: data from the PROWESS trial.  Intensive Care Med. 2003;  29 894-903
  • 74 Vincent J L, Bernard G R, Beale R. et al . Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: Further evidence for survival and safety and implications for early treatment.  Crit Care Med. 2005;  33 2266-2277
  • 75 Abraham E, Laterre P F, Talwar D. et al . Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.  N Engl J Med. 2005;  353 1332-1341
  • 76 Levi M, Levy M, Williams M D. et al . Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated).  Am J Respir Crit Care Med. 2007;  176 483-490
  • 77 The NHLBI ARDS Network . Comparison of two fluid-management strategies in acute lung Injury.  N Engl J Med. 2006;  354 2564-2575

Prof. Dr. med. Joachim Lorenz

Klinik für Pneumologie, Internistische Intensivmedizin, Infektiologie und Schlafmedizin
Klinikum Lüdenscheid

Paulmannshöher Straße 14
58515 Lüdenscheid

eMail: joachim.lorenz@klinikum-luedenscheid.de