Standards in der Diagnostik und Therapie der Sepsis

Einleitung

Sepsis, septischer Schock und sepsis-induziertes Multiorganversagen haben den höchsten Anteil an der Mortalität von Patienten auf operativen Intensivstationen [1] [2]. Trotz vieler Weiterentwicklungen auf dem Gebiet der Intensivmedizin hat sich die Letalität der Sepsis (35 - 70 %) in den letzten Jahren nicht wesentlich geändert [3].

Die verschiedenen Aspekte der Pathophysiologie bei Sepsis sind Thema unzähliger Untersuchungen und Veröffentlichungen der letzten Jahre. Obwohl viele dieser Erkenntnisse dazu beigetragen haben, das Krankheitsbild der Sepsis besser zu verstehen, haben bislang nur wenige dieser Einsichten in die Pathophysiologie auch neue oder verbesserte Therapieansätze hervorgebracht. So sind das Zusammenspiel und die Bedeutung der verschiedenen Mediatoren des inflammatorischen Systems heute wesentlich besser bekannt. Sich daraus ergebende therapeutische Optionen liegen jedoch nur wenige vor.

Literatur

• 1 From the Centers for Disease Control . Increase in National Hospital Discharge Survey rates for septicemia - United States, 1979 - 1987.  JAMA. 1990;  263 937-938
• 2 Sands K E, Bates D W, Lanken P N, Graman P S, Hibberd P L, Kahn K L, Parsonnet J, Panzer R, Orav E J, Snydman D R. Epidemiology of sepsis syndrome in 8 academic medical centers. Academic Medical Center Consortium Sepsis Project Working Group.  JAMA. 1997;  278 234-240
• 3 Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment.  Crit Care Med. 1997;  25 1095-1100
• 4 Schottmüller H. Wesen und Behandlung der Sepsis. Verhandl Dt Kongress Inn Med 1914: 257-280
• 5 Gramm H J, Reinhart K. Sepsis und septischer Schock - Definition und Epidemiologie. In: Van Aken H, Reinhart K, Zimpfer M, (eds) ains Band 2: Intensivmedizin. Stuttgart, New York; Thieme 2001: 756-760
• 6 Bone R C, Balk R A, Cerra F B, Dellinger R P, Fein A M, Knaus W A, Schein R M, Sibbald W J. 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 1644-1655
• 7 Rangel Frausto M S, Pittet D, Costigan M, Hwang T, Davis C S, Wenzel R P. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study.  JAMA. 1995;  273 117-123
• 8 Rau B, Steinbach G, Gansauge F, Mayer J M, Grunert A, Beger H G. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis.  Gut. 1997;  41 832-840
• 9 Selberg O, Hecker H, Martin M, Klos A, Bautsch W, Kohl J. Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6.  Crit Care Med. 2000;  28 2793-2798
• 10 de Werra I, Jaccard C, Corradin S B, Chiolero R, Yersin B, Gallati H, Assicot M, Bohuon C, Baumgartner J D, Glauser M P, Heumann D. Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.  Crit Care Med. 1997;  25 607-613
• 11 Wanner G A, Keel M, Steckholzer U, Beier W, Stocker R, Ertel W. Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients.  Crit Care Med. 2000;  28 950-957
• 12 Lundberg J S, Perl T M, Wiblin T, Costigan M D, Dawson J, Nettleman M D, Wenzel R P. Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units.  Crit Care Med. 1998;  26 1020-1024
• 13 Connors A F, Speroff T, Dawson N V, Thomas C, Harrell F E, Wagner D, Desbiens N, Goldman L, Wu A W, Califf R M, Fulkerson W J, Vidaillet H, Broste S, Bellamy P, Lynn J, Knaus W A. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.  JAMA. 1996;  276 889-897
• 14 von Spiegel T, Wietasch G, Bursch J, Hoeft A. HZV-Bestimmung mittels transpulmonaler Thermodilution. Eine Alternative zum Pulmonaliskatheter?.  Anaesthesist. 1996;  45 1045-1050
• 15 Shoemaker W C, Appel P L, Kram H B, Waxman K, Lee T S. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.  Chest. 1988;  94 1176-1186
• 16 Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output and oxygen delivery improves outcome in septic shock.  Chest. 1992;  102 216-220
• 17 Tuchschmidt J, Fried J, Swinney R, Sharma O P. Early hemodynamic correlates of survival in patients with septic shock.  Crit Care Med. 1989;  17 719-723
• 18 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. SvO₂ Collaborative Group.  N Engl J Med. 1995;  333 1025-1032
• 19 Heyland D K, Cook D J, King D, Kernerman P, Brun Buisson C. Maximizing oxygen delivery in critically ill patients: a methodologic appraisal of the evidence.  Crit Care Med. 1996;  24 517-524
• 20 Hayes M A, Timmins A C, Yau E H, Palazzo M, Hinds C J, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients.  N Engl J Med. 1994;  330 1717-1722
• 21 Desjars P, Pinaud M, Potel G, Tasseau F, Touze M D. A reappraisal of norepinephrine therapy in human septic shock.  Crit Care Med. 1987;  15 134-137
• 22 Desjars P, Pinaud M, Bugnon D, Tasseau F. Norepinephrine therapy has no deleterious renal effects in human septic shock.  Crit Care Med. 1989;  17 426-429
• 23 Hesselvik J F, Brodin B. Low dose norepinephrine in patients with septic shock and oliguria: effects on afterload, urine flow, and oxygen transport.  Crit Care Med. 1989;  17 179-180
• 24 Martin C, Eon B, Saux P, Aknin P, Gouin F. Renal effects of norepinephrine used to treat septic shock patients.  Crit Care Med. 1990;  18 282-285
• 25 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock.  N Engl J Med. 2001;  345 1368-1377
• 26 Bisonni R S, Holtgrave D R, Lawler F, Marley D S. Colloids versus crystalloids in fluid resuscitation: an analysis of randomized controlled trials.  J Fam Pract. 1991;  32 387-390
• 27 Velanovich V. Crystalloid versus colloid fluid resuscitation: a meta-analysis of mortality.  Surgery. 1989;  105 65-71
• 28 Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: A systematic review of randomised trials.  BMJ. 1998;  316 961-964
• 29 Roberts I. Human albumin administration in critically ill patients: systematic review of randomised controlled trials.  Br Med J. 1998;  317 235-240
• 30 Third European Consensus Conference in Intensive Care Medicine . Tissue hypoxia: How to detect, how to correct, how to prevent. Societe de Reanimation de Langue Francaise. The American Thoracic Society. European Society of Intensive Care Medicine.  Am J Respir Crit Care Med. 1996;  154 1573-1578
• 31 Hébert P C, Wells G, Blajchman M A, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.  N Engl J Med. 1999;  340 409-417
• 32 Marik P E, Sibbald W J. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.  JAMA. 1993;  269 3024-3029
• 33 Bersten A D, Hersch M, Cheung H, Rutledge F S, Sibbald W J. The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis.  Surgery. 1992;  112 549-561
• 34 Vincent J L, van der Linden P, Domb M, Blecic S, Azimi G, Bernard A. Dopamine compared with dobutamine in experimental septic shock: relevance to fluid administration.  Anesth Analg. 1987;  66 565-571
• 35 Gutierrez G, Clark C, Brown S D, Price K, Ortiz L, Nelson C. Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.  Am J Respir Crit Care Med. 1994;  150 324-329
• 36 Silverman H J, Tuma P. Gastric tonometry in patients with sepsis. Effects of dobutamine infusions and packed red blood cell transfusions.  Chest. 1992;  102 184-188
• 37 Levy B, Bollaert P E, Lucchelli J P, Sadoune L O, Nace L, Larcan A. Dobutamine improves the adequacy of gastric mucosal perfusion in epinephrine-treated septic shock.  Crit Care Med. 1997;  25 1649-1654
• 38 Neviere R, Mathieu D, Chagnon J L, Lebleu N, Wattel F. The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients.  Am J Respir Crit Care Med. 1996;  154 1684-1688
• 39 Joly L M, Monchi M, Cariou A, Chiche J D, Bellenfant F, Brunet F, Dhainaut J F. Effects of dobutamine on gastric mucosal perfusion and hepatic metabolism in patients with septic shock.  Am J Respir Crit Care Med. 1999;  160 1983-1986
• 40 Reinelt H, Radermacher P, Fischer G, Geisser W, Wachter U, Wiedeck H, Georgieff M, Vogt J. Effects of a dobutamine-induced increase in splanchnic blood flow on hepatic metabolic activity in patients with septic shock.  Anesthesiology. 1997;  86 818-824
• 41 Duke G J, Briedis J H, Weaver R A. Renal support in critically ill patients: low-dose dopamine or low-dose dobutamine?.  Crit Care Med. 1994;  22 1919-1925
• 42 Shoemaker W C, Appel P L, Kram H B. Oxygen transport measurements to evaluate tissue perfusion and titrate therapy: dobutamine and dopamine effects.  Crit Care Med. 1991;  19 672-688
• 43 Meier-Hellmann A, Reinhart K. Cardiovascular support by hemodynamic subset: Sepsis. In: Pinsky MR (ed.) Applied Cardiovascular Physiology. Springer-Verlag, Berlin 1997: 230-245
• 44 Bollaert P E, Bauer P, Audibert G, Lambert H, Larcan A. Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine-resistant septic shock.  Chest. 1990;  98 949-953
• 45 Moran J L, O'Fathartaigh M S, Peisach A R, Chapman M J, Leppard P. Epinephrine as an inotropic agent in septic shock: a dose-profile analysis.  Crit Care Med. 1993;  21 70-77
• 46 Meier-Hellmann A, Reinhart K, Bredle D L, Specht M, Spies C D, Hannemann L. Epinephrine impairs splanchnic perfusion in septic shock.  Crit Care Med. 1997;  25 399-404
• 47 Levy B, Bollaert P E, Charpentier C, Nace L, Audibert G, Bauer P, Nabet P, Larcan A. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: A prospective, randomized study.  Intensive Care Med. 1997;  23 282-287
• 48 Lherm T, Troche G, Rossignol M, Bordes P, Zazzo J F. Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines.  Intensive Care Med. 1996;  22 213-219
• 49 Giraud G D, MacCannell K L. Decreased nutrient blood flow during dopamine- and epinephrine-induced intestinal vasodilation.  J Pharmacol Exp Ther. 1984;  230 214-220
• 50 Meier-Hellmann A, Bredle D L, Specht M, Spies C, Hannemann L, Reinhart K. The effects of low dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock.  Intensive Care Med. 1997;  23 31-37
• 51 van den Berghe G, de Zegher F. Anterior pituitary function during critical illness and dopamine treatment.  Crit Care Med. 1996;  24 1580-1590
• 52 Marik P E, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis.  JAMA. 1994;  272 1354-1357
• 53 Hannemann L, Reinhart K, Grenzer O, Meier-Hellmann A, Bredle D L. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock.  Crit Care Med. 1995;  23 1962-1970
• 54 Hollenberg S M, Ahrens T S, Astiz M E, Chalfin D B, Dasta J F, Heard S O, Martin C, Susla G M, Vincent J L. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis.  Crit Care Med. 1999;  27 639-660
• 55 Sprung C L, Bernard G R, Dellinger R P. Guidelines for the management of severe sepsis and septic shock.  Intensive Care Med. 2001;  27 1-134
• 56 Leier C V. Regional blood flow responses to vasodilators and inotropes in congestive heart failure.  Am J Cardiol. 1988;  62 86E-93E
• 57 Kiefer P, Tugtekin I, Wiedeck H, Bracht H, Geldner G, Georgieff M, Radermacher P. Effect of a dopexamine-induced increase in cardiac index on splanchnic hemodynamics in septic shock.  Am J Respir Crit Care Med. 2000;  161 775-779
• 58 Cain S M, Curtis S E. Systemic and regional oxygen uptake and delivery and lactate flux in endotoxic dogs infused with dopexamine.  Crit Care Med. 1991;  19 1552-1560
• 59 Temmesfeld-Wollbrück B, Szalay A, Mayer K, Olschewski H, Seeger W, Grimminger F. Abnormalities of gastric mucosal oxygenation in septic shock: Partial responsiveness to dopexamine.  Am J Respir Crit Care Med. 1998;  157 1586-1592
• 60 Scheeren T W, Schwarte L A, Loer S A, Picker O, Fournell A. Dopexamine but not dopamine increases gastric mucosal oxygenation during mechanical ventilation in dogs.  Crit Care Med. 2002;  30 881-887
• 61 Tighe D, Moss R, Heywood G, al Saady N, Webb A, Bennett D. Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis.  Crit Care Med. 1995;  23 1997-2007
• 62 Lund N, de Asla R J, Cladis F, Papadakos P J, Thorborg P A. Dopexamine hydrochloride in septic shock: effects on oxygen delivery and oxygenation of gut, liver, and muscle.  J Trauma. 1995;  38 767-775
• 63 Schmidt H, Secchi A, Wellmann R, Bach A, Bhrer H, Martin E. Dopexamine maintains intestinal villus blood flow during endotoxemia in rats.  Crit Care Med. 1996;  24 1233-1237
• 64 Smithies M, Yee T H, Jackson L, Beale R, Bihari D. Protecting the gut and the liver in the critically ill: effects of dopexamine.  Crit Care Med. 1994;  22 789-795
• 65 Maynard N D, Bihari D J, Dalton R N, Smithies M N, Mason R C. Increasing splanchnic blood flow in the critically III.  Chest. 1995;  108 1648-1654
• 66 Meier-Hellmann A, Bredle D L, Specht M, Hannemann L, Reinhart K. Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine.  Crit Care Med. 1999;  27 2166-2171
• 67 Uusaro A, Ruokonen E, Takala J. Gastric mucosal pH does not reflect changes in splanchnic blood flow after cardiac surgery.  Br J Anaesth. 1995;  74 149-154
• 68 Levy B, Nace L, Bollaert P E, Dousset B, Mallie J P, Larcan A. Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock.  Intensive Care Med. 1999;  25 942-948
• 69 Kern H, Schroder T, Kaulfuss M, Martin M, Kox W J, Spies C D. Enoximone in contrast to dobutamine improves hepatosplanchnic function in fluid-optimized septic shock patients.  Crit Care Med. 2001;  29 1519-1525
• 70 O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock.  Lancet. 2002;  359 1209-1210
• 71 Dunser M W, Mayr A J, Ulmer H, Ritsch N, Knotzer H, Pajk W, Luckner G, Mutz N J, Hasibeder W R. The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis.  Anesth Analg. 2001;  93 7-13
• 72 Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura M, Nakano Y, Boyle W A. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock.  Crit Care Med. 2001;  29 487-493
• 73 Holmes C L, Walley K R, Chittock D R, Lehman T, Russell J A. The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series.  Intensive Care Med. 2001;  27 1416-1421
• 74 Patel B M, Chittock D R, Russell J A, Walley K R. Beneficial effects of short-term vasopressin infusion during severe septic shock.  Anesthesiology. 2002;  96 576-582
• 75 Landry D W, Levin H R, Gallant E M, Ashton R C , Seo S, D'Alessandro D, Oz M C, Oliver J A. Vasopressin deficiency contributes to the vasodilation of septic shock.  Circulation. 1997;  95 1122-1125
• 76 Varga C, Pavo I, Lamarque D, Szepes Z, Kiss J, Karacsony G, Laszlo F A, Laszlo F. Endogenous vasopressin increases acute endotoxin shock-provoked gastrointestinal mucosal injury in the rat.  Eur J Pharmacol. 1998;  352 257-261
• 77 Klinzing S, Schiergens V, Reinhart K, Meier-Hellmann A. Could vasopressin be an alternative for vasopressor therapy in sepsis?.  Eur J Anaesthesiol. 2002 ;  19 (Suppl. 24) 169
• 78 Hannemann L, Korell R, Meier-Hellmann A, Reinhart K. Hypertone Losungen auf der Intensivstation.  Zentralbl Chir. 1993;  118 245-249
• 79 Kreimeier U, Frey L, Dentz J, Herbel T, Messmer K. Hypertonic saline dextran resuscitation during the initial phase of acute endotoxemia: effect on regional blood flow.  Crit Care Med. 1991;  19 801-809
• 80 Kreimeier U, Messmer K. Zum Einsatz hypertoner Kochsalzlösungen in der Intensiv- und Notfallmedizin - Entwicklungen und Perspektiven.  Klin Wochenschr. 1991;  69 (Suppl 26) 134-142
• 81 Kiefer P, Tugtekin I, Wiedeck H, Bracht H, Vogt J, Wachter U, Weiss M, Altin C, Georgieff M, Radermacher P. Hepato-splanchnic metabolic effects of the stable prostacyclin analogue iloprost in patients with septic shock.  Intensive Care Med. 2001;  27 1179-1186
• 82 Lehmann C, Taymoorian K, Wauer H, Krausch D, Birnbaum J, Kox W J. Effects of the stable prostacyclin analogue iloprost on the plasma disappearance rate of indocyanine green in human septic shock.  Intensive Care Med. 2000;  26 1557-1560
• 83 Scheeren T, Radermacher P. Prostacyclin (PGI2): new aspects of an old substance in the treatment of critically ill patients.  Intensive Care Med. 1997;  23 146-158
• 84 Reinhart K, Spies C D, Meier-Hellmann A, Bredle D L, Hannemann L, Specht M, Schaffartzik W. N-acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation.  Am J Respir Crit Care Med. 1995;  151 773-779
• 85 Spies C D, Reinhart K, Witt I, Meier-Hellmann A, Hannemann L, Bredle D L, Schaffartzik W. 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 1738-1746
• 86 Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier-Hellmann A, Spies C. N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study.  Crit Care Med. 2000;  28 3799-3807
• 87 Rubanyi G M, Vanhoutte P M. Superoxide anions and hyperoxia inactivate endotheliumderived relaxing factor.  Am J Physiol. 1986;  250 H 822-H 827
• 88 Harrison P M, Wendon J A, Gimson A E, Alexander G J, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure.  N Engl J Med. 1991;  324 1852-1857
• 89 Aruoma O I, Halliwell B, Hoey B M, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid.  Free Radic Biol Med. 1989;  6 593-597
• 90 Allman K G, Stoddart A P, Kennedy M M, Young J D. L-arginine augments nitric oxide production and mesenteric blood flow in ovine endotoxemia.  Am J Physiol. 1996;  271 H 1296-H 1301
• 91 Petros A, Bennett D, Vallance P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.  Lancet. 1991;  338 1557-1558
• 92 Wright C E, Rees D D, Moncada S. Protective and pathological roles of nitric oxide in endotoxin shock.  Cardiovasc Res. 1992;  26 48-57
• 93 Cobb J P, Natanson C, Quezado Z M, Hoffman W D, Koev C A, Banks S, Correa R, Levi R, Elin R J, Hosseini J M. Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs.  Am J Physiol. 1995;  268 H 1634-H 1642
• 94 Schneider F, Lutun P, Hasselmann M, Stoclet J C, Tempe J D. Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations.  Intensive Care Med. 1992;  18 309-311
• 95 Brown G, Frankl D, Phang T. Continuous infusion of methylene blue for septic shock.  Postgrad Med J. 1996;  72 612-614
• 96 Zaloga G P. Early enteral nutritional support improves outcome: hypothesis or fact?.  Crit Care Med. 1999;  27 259-261
• 97 Heyland D K, Cook D J, Guyatt G H. Enteral nutrition in the critically ill patient: a critical review of the evidence.  Intensive Care Med. 1993;  19 435-442
• 98 Marik P E, Zaloga G P. Early enteral nutrition in acutely ill patients: a systematic review.  Crit Care Med. 2001;  29 2264-2270
• 99 Griffiths R D, Jones C, Palmer T E. Six-month outcome of critically ill patients given glutamine- supplemented parenteral nutrition.  Nutrition. 1997;  13 295-302
• 100 Roth E, Spittler A, Oehler R. Glutamin: Wirkungen auf das Immunsystem, auf Eiweisshaushalt und Darmfunktionen.  Wien Klin Wochenschr. 1996;  108 669-676
• 101 Kemen M, Senkal M, Homann H H, Mumme A, Dauphin A K, Baier J, Windeler J, Neumann H, Zumtobel V. Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.  Crit Care Med. 1995;  23 652-659
• 102 Daly J M, Lieberman M D, Goldfine J, Shou J, Weintraub F, Rosato E F, Lavin P. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome.  Surgery. 1992;  112 56-67
• 103 Heyland D K, Cook D J, Guyatt G H. Does the formulation of enteral feeding products influence infectious morbidity and mortality rates in the critically ill patients? A critical review of the evidence.  Crit Care Med. 1994;  22 1192-1202
• 104 Beale R J, Bryg D J, Bihari D J. Immunonutrition in the critically ill: a systematic review of clinical outcome.  Crit Care Med. 1999;  27 2799-2805
• 105 Bone R C, Fisher C J, Clemmer T P, Slotman G J, Metz C A, Balk R A. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.  N Engl J Med. 1987;  317 653-658
• 106 The Veterans Administration Systemic Sepsis Cooperative Study Group . Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis.  N Engl J Med. 1987;  317 659-665
• 107 Bollaert P E, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone.  Crit Care Med. 1998;  26 645-650
• 108 Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.  Crit Care Med. 1999;  27 723-732
• 109 Briegel J, Kellermann W, Forst H, Haller M, Bittl M, Hoffmann G E, Buchler M, Uhl W, Peter K. Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group.  Clin Investig. 1994;  72 782-787
• 110 Annane D. Effects of the combination of hydrocortisone (HC) - fludrocortisone (FC) on mortality in septic shock. JAMA 2002
• 111 Grootendorst A F, van Bommel E F. The role of hemofiltration in the critically-ill intensive care unit patient: present and future.  Blood Purif. 1993;  11 209-223
• 112 Grootendorst A F, van Bommel E F, van Leengoed L A, van Zanten A R, Huipen H J, Groeneveld A B. Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs.  J Crit Care. 1993;  8 161-169
• 113 Grootendorst A F, van Bommel E F, van der Hoven B, van Leengoed L A, van Osta A L. High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig.  Intensive Care Med. 1992;  18 235-240
• 114 Lee P A, Matson J R, Pryor R W, Hinshaw L B. Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine.  Crit Care Med. 1993;  21 914-924
• 115 Lange R, Erhard J, Sander A, Scherer R, Eigler F. Der Einsatz der kontinuierlichen veno-venösen Hochvolumen-Hämofiltration (CVVHVH) bei Patienten im Multiorganversagen. Prinzip und Anwendung.  Zentralbl Chir. 1996;  121 535-540
• 116 Storck M, Hartl W H, Zimmerer E, Inthorn D. Comparison of pump-driven and spontaneous continuous haemofiltration in postoperative acute renal failure.  Lancet. 1991;  337 452-455
• 117 Cole L, Bellomo R, Hart G, Journois D, Davenport P, Tipping P, Ronco C. A phase II randomized, controlled trial of continuous hemofiltration in sepsis.  Crit Care Med. 2002;  30 100-106
• 118 Ullrich H, Jakob W, Frohlich D, Rothe G, Prasser C, Drobnik W, Taeger K, Meier-Hellmann A, Reinhart K, Zimmermann M, Schmitz G. A new endotoxin adsorber: first clinical application.  Ther Apher. 2001;  5 326-334
• 119 Casey L C, Balk R A, Bone R C. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome.  Ann Intern Med. 1993;  119 771-778
• 120 Debets J M, Kampmeijer R, van der Linden M P, Buurman W A, van der Linden C J. Plasma tumor necrosis factor and mortality in critically ill septic patients.  Crit Care Med. 1989;  17 489-494
• 121 Beutler B, Milsark I W, Cerami A C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin.  Science. 1985;  229 869-871
• 122 Tracey K J, Fong Y, Hesse D G, Manogue K R, Lee A T, Kuo G C, Lowry S F, Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia.  Nature. 1987;  330 662-664
• 123 Panacek E A, Marshall J, Fischkoff S, Barchuk W, Teoh L. Neutralization of TNF by a monoclonal antibody improves survival and reduces organ dysfunction in human sepsis: Results of the MONARC trial.  Chest. 2000;  118 S88
• 124 Warren B L, Eid A, Singer P, Pillay S S, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke H O, Heinrichs H, Schindel F, Juers M, Bone R C, Opal S M. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.  JAMA. 2001;  286 1869-1878
• 125 Bernard G R, Vincent J L, Laterre P F, LaRosa S P, Dhainaut J F, Lopez-Rodriguez A, Steingrub J S, Garber G E, Helterbrand J D, Ely E W, Fisher C J. Efficacy and safety of recombinant human activated protein C for severe sepsis.  N Engl J Med. 2001;  344 699-709
• 126 Alejandria M M, Langsang M A, Dans L F. Intravenous immunglobulin for treating sepsis and septic shock.  The Cochrane Library 2.. 2001;  Oxford Update Software
• 127 Callaham M L, Wears R L, Weber E J, Barton C, Young G. Positive-outcome bias and other limitations in the outcome of research abstracts submitted to a scientific meeting.  JAMA. 1998;  280 254-257
• 128 Easterbrook P J, Berlin J A, Gopalan R, Matthews D R. Publication bias in clinical research.  Lancet. 1991;  337 867-872
• 129 Werdan K, Pilz G . Polyvalent immune globulins.  Shock. 1987;  7 (5) 1918
• 130 Sibbald W J, Vincent J L. Round table conference on clinical trials for the treatment of sepsis.  Crit Care Med. 1995;  23 394-399
• 131 Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J, Dubin A, Schiavi E, Jorge M, Pusajo J. Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.  Lancet. 1992;  339 195-199