Recent developments in the treatment of sepsis

Bibliography

• CENTER FOR DISEASE CONTROL: Increase in national hospital discharge survey rates for septicemia: United States, 1979-1989. MMRW Morb. Modal. Wkly Rep. (1990) 39:31–34.
   PubMedGoogle Scholar
• RIEDMAN G, SILVA E, VINCENT JL: Has the mortality of septic shock changed with time? Grit. Care Med. (1998) 26(12):2078–2086.
   Google Scholar
• AGNUS DC, BIRMINGHAM MC, BALK RA et al.: E5 murine monoclonal antiendotoxin antibody in Gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA (2000) 283(13):1723–1730.
   Google Scholar
• MCCLOSKEY RV, STRAUBE RC, SANDERS C, SMITH SM, SMITH CR: Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group. Ann. Intern. Med. (1994) 121(1):1–5.
   PubMed Web of Science ®Google Scholar
• DERKX B, WITTES J, MCCLOSKEY R: Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group. Chh. Infect. Dis. (1999) 28(4):770–777.
   Google Scholar
• GIROIR BP, QUINT PA, BARTON P et al.: Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet (1997) 350(9089):1439–1443.
   PubMed Web of Science ®Google Scholar
• 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(9234):961–967.
   Google Scholar
• LETURCQ DJ, MORIARTY AM, TALBOTT G, WINN RK, MARTIN TR, ULEVITCH RJ: Antibodies against CD14 protect primates from endotoxin-induced shock. J. Chu. Invest. (1996) 98(7):1533–1538.
   PubMed Web of Science ®Google Scholar
• VERBON A, DEKKERS PE, TEN HOVE T et al.: IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans. J. Immurrol. (2001) 166(5):3599–3605.
   Google Scholar
• CHOW JC, YOUNG DW, GOLENBOCK DT et al.: Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. _J. Biol. Chem. (1999) 274:10689–10692.
   PubMed Web of Science ®Google Scholar
• BUNNELL E, LYNN M, HABET K et al.: A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia. Grit. Care Med. (2000) 28:2713–2720.
   PubMed Web of Science ®Google Scholar
• GOLDFARB RD, PARKER TS, LEVINE DM et al.: Phospholipid rich emulsion improved survival and cardiovascular status in porcine septic shock in a dose-dependent manner. Grit. Care Med. (1999) 27:A158 (Abstract).
   Google Scholar
• ABRAHAM E, WUNDERINK R, SILVERMAN H et al.: Efficacy and safety of monoclonal antibody to human tumour necrosis factor-alpha in patients with sepsis syndrome: a randomized, controlled, double-blind, multicenter clinical trial. JAMA (1995) 273:934–941.
   PubMed Web of Science ®Google Scholar
• COHEN J, CARLET J, THE INTERSEPT STUDY GROUP: INTERSEPT: An international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor [alpha] in patients with sepsis. Grit. Care Med. (1996) 24:1431–1440.
   PubMed Web of Science ®Google Scholar
• ABRAHAM E, ANZUETO A, GUTIERREZ G etal: Double-blind randomized controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. Lancet (1998) 351:929–933.
   PubMed Web of Science ®Google Scholar
• REINHART K, WIEGEND-LOHNERT C, GRIMMINGER F et al.: Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK195F, in patients with sepsis and septic shock: A multicenter, randomized, placebo-controlled, dose-ranging study. Grit. Care Med. (1996) 24:733–742.
   PubMed Web of Science ®Google Scholar
• PANACEK EA, 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.):885 (Abstract).
   Google Scholar
• •Preliminary study report suggesting that afelimomab treatment improves survival in patients with severe sepsis.
   Google Scholar
• FISHER CJ Jr, 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 Biagi J. Med. (1996) 334:1697–1702.
   Google Scholar
• ABRAHAM E, GLAUSER MP, BUTLER T et al.: p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. JAMA (1997) 277:1531–1538.
   PubMed Web of Science ®Google Scholar
• 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. Grit Care Med. (2001) 29(3):503–510.
   PubMed Web of Science ®Google Scholar
• KHADAROO RG, ROTSTEIN OD, MARSHALL JC: Neutralizing tumor necrosis factor in the treatment of sepsis and septic shock: a meta-analysis. Grit. Care Med. (1999) 29:A19 (Abstract).
   Google Scholar
• •A meta-analysis of eleven clinical trials using antiTNE therapy in patients with sepsis.
   Google Scholar
• JOHN S, GREISBACH D, BAUMGARTEL M, WEIHPRECHT H, SCHMIEDER RE, GEIGER H: Effects of continuous haemofiltration versus intermittent haemodialysis on systemic haemodynamicsand splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial. Nephrol. Dial. Transplarm (2001) 16(2):320–327.
   PubMed Web of Science ®Google Scholar
• KELLUM JA, JOHNSON JP, KRAMER Det al: Diffusive versus convective therapy: effects on mediators of inflammation in patients with severe systemic inflammatory response syndrome. Gilt. Care Med. (1998) 26:1995–2000.
   PubMed Web of Science ®Google Scholar
• HEERING E MORGERA S, SCHMITZ FJ etal.: Cytokine removal and cardiovascular hemodynamics in septic patients with continuous hemofiltration. Intensive Care Med. (1997) 23:288–296.
   PubMed Web of Science ®Google Scholar
• COLE L, BELLOMOR, HART G etal.: A Phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit. Care Med. (2002) 30(10):100–106.
   Google Scholar
• COLE L, BELLOMO R, JOURNOIS D et al.: High-volume haemofiltration in human septic shock. Intensive Care Med. (2001) 27(6):978–986.
   PubMed Web of Science ®Google Scholar
• DE VRIESE AS, COLARDYN FA, PHILIPPE JJ, VANHOLDER RC, DE SUTTER JH, LAMEIRE NH: Cytokine removal during continuous hemofiltration in septic patients. J. Am. Soc. Nephrol. (1999) 10(4):846–853.
   PubMed Web of Science ®Google Scholar
• RONCO C, BRENDOLAN A, LONNEMANN G et al: A pilot study of coupled plasma filtration with adsorption in septic shock. Grit. Care Med. (2002) 30(6):1250–1255.
   PubMed Web of Science ®Google Scholar
• •Unique study that suggests that blood purification restores impaired leukocyte responsiveness that occurs during sepsis.
   Google Scholar
• TETTA C, BELLOMO R, BRENDOLAN A et aL: Use of adsoprtive mechanisms in continuous renal replacement therapies in the critically ill. Kidney Irm (1999) 56\(Suppl. 72):515–519.
   Google Scholar
• WANG Y, LIU Y, SARKER KP etal.: Polymyxin B binds to anandamide and inhibits its cytotoxic effect. FEBS Lett. (2000) 470(2):151–155.
   Google Scholar
• AOKI H, KODANIA M, TANI T, HANASAWA K: Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. Am. Surg. (1994) 167(4):412–417.
   Google Scholar
• TANI T, HANASAWA K, ENDO Y et al.: Therapeutic apheresis for septic patients with organ dysfunction: hemoperfusion using a polymyxin B immobilized column. Artif Organs (1998) 22(12):1038–1044.
   PubMed Web of Science ®Google Scholar
• NAKANIURA T, EBIHARA L, SHIMADA N etal.: Effects of hemoperfusion with polymyxin B-immobilized fibre on serum neopterin and soluble interleukin-2 receptor concentrations in patients with septic shock. J. Infect. (1998) 37(3):241–247.
   Google Scholar
• NAKANIURA T, EBIHARA I, SHOJI H, USHIYANIA C, SUZUKI S, KOIDE H: Treatment with polymyxin B-immobilized fiber reduces platelet activation in septic shock patients: decrease in plasma levels of soluble P-selectin, platelet factor 4 and beta-thromboglobulin. Inllamm. Res. (1999) 48(4):171–175.
   PubMed Web of Science ®Google Scholar
• NEMOTO H, NAKAMOTO H, OKADA H et al: Newly developed immobilized polymyxin B fibers improve the survival of patients with sepsis. Bkoc1Purif (2001) 19(4):361–368.
   Google Scholar
• •This study suggests that early treatment (i.e. in patients with lower APACHE II scores) using PMX-F filters improves outcome in sepsis.
   Google Scholar
• ZIMMERMANN M, BUSCH K, KUHN S, ZEPPERZAUER M: Endotoxin adsorbent based on immobilized human serum albumin. Chu. Chem. Lab. Med. (1999) 37(3):373–379.
   PubMed Web of Science ®Google Scholar
• ULLRICH H, JAKOB W, FROHLICH D etal.: A new endotoxin adsorber: first clinical application. Ther. Apher (2001) 5(5):326–334.
   Google Scholar
• TSUCHIDA K, TAKEMOTO Y, NAKANIURA T et al: Lixelle adsorbent to remove inflammatory cytokines. Artif Organs (1998) 22(12):1064–1067.
   PubMed Web of Science ®Google Scholar
• TSUCHIDA K, TAKEMOTO Y, NAKAMURA T etal.: Adsorption of microorganism components by lixelle beads. Artif Organs (2000) 24(7):577–580.
   Google Scholar
• CHANDY T, RAO GH: Evaluation of heparin immobilized chitosan-PEG microbeads for charcoal encapsulation and endotoxin removal. Artif Cells Blood Substit. Immobil. Biotechnol. (2000) 28(1):65–77.
   PubMed Web of Science ®Google Scholar
• YOKOTA H, KIYONAGA H, KANIWA H, SAISHO N: Adsorption of endotoxin on glass in the presence of rhIL-11. Pharm. Biomed. Anal. (2000) 22(5):757–761.
   PubMed Web of Science ®Google Scholar
• NUIJENS JH, EERENBERG-BELMER AJ, HUIJBREGTS CC etal.: Proteolytic inactivation of plasma Cl-inhibitor in sepsis. J. Chu. Invest. (1989) 84(2):443–450.
   Google Scholar
• FRONHOFFS S, LUYKEN J, STEUER K, HANSIS M, VETTER H, WALGER P: The effect of Cl-esterase inhibitor in definite and suspected streptococcal toxic shock syndrome. Report of seven patients. Intensive Care Med. (2000) 26(10):1566–1570.
   PubMed Web of Science ®Google Scholar
• CALIEZI C, ZEERLEDER S, REDONDO M et al.: Cl-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction. Grit. Care Med. (2002) 30:1722–1728.
   PubMed Web of Science ®Google Scholar
• CZERNIAK BJ, SARMA V, PIERSON CL et al.: Protective effects of C5a blockade in sepsis. Nat. Med. (1999) 5(7):788–792.
   PubMed Web of Science ®Google Scholar
• HUBER-LANG M, SARMA VJ, LU KT et al.: Role of C5a in multiorgan failure during sepsis. J. Immune]. (2001) 166(2):1193–1199.
   PubMed Web of Science ®Google Scholar
• HUBER-LANG MS, SARMA VJ, MCGUIRE SR et al.: Protective effects of anti-05a peptide antibodies in experimental sepsis. FASEB (2001) 15(3)568–570.
   Google Scholar
• STAUBACH KH, SCHRODER J, STUBER F, GEHRKE K, TRAUMANN E, ZABEL P: Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study. Arch. Surg. (1998) 133(1):94–100.
   PubMed Web of Science ®Google Scholar
• WENISCH C, LOOAREESUWAN S, WILAIRATANA P etal.: Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria. Am. J. Trap. Med. Hyg. (1998) 58(30):343–347.
   Google Scholar
• LAUTERBACH R, ZEMBALA M: Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis. Eur. Pediatr. (1996) 155(5):404–409.
   PubMed Web of Science ®Google Scholar
• LAUTERBACH R, PAWLIK D, KOWALCZYK D, KSYCINSKI W, HELWICH E, ZEMBALA M: Effect of the immunomodulating agent, pentoxifylline in the treatment of sepsis in premature infants: a placebo-controlled, double-blind trial. Grit. Care Med. (1999) 27(4):807–814.
   PubMed Web of Science ®Google Scholar
• •Study demonstrating an apparent beneficial effect of intravenous pentoxifylline in reducing cytokine levels and improving clinical outcome in septic premature infants.
   Google Scholar
• HELLER S, WEBER K, HELLER A et al.: Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia. Grit. Care Med. (1999) 27:756–763.
   PubMed Web of Science ®Google Scholar
• DHAINAUT JF, TENAILLON A, LE TULZO Y: Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomised, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group. Grit. Care Med. (1994) 22(10:1720–1728.
   Google Scholar
• DHAINAUT JF, TENAILLON A, HEMMER M: 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. Grit. Care Med. (1998) 26(12):1963–1971.
   Google Scholar
• SUPUTTAMONGKOL Y, INTARANONGPAI S, SMITH MD: A double-blind placebo-controlled study of an infusion of lexipafant (Platelet-activating factor receptor antagonist) in patients with severe sepsis. Antimicrob. Agents Chemother. (2000) 44(3):693–696.
   PubMed Web of Science ®Google Scholar
• 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. Grit. Care Med. (2000) 28(3):638–642.
   PubMed Web of Science ®Google Scholar
• FROON AM, GREVE JW, BUURMAN WA: Treatment with the platelet-activating factor antagonist TCV-309 in patients with severe systemic inflammatory response syndrome: a prospective, multi-center, double-blind, randomized Phase II trial. Shock (1996) 5(5):313–319.
   PubMed Web of Science ®Google Scholar
• POEZE M, FROON AH, RAMSAY G, BUURMAN WA, GREVE JW: Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized Phase II trial. TCV-309 Septic Shock Study Group. Shock (2000) 14(4):421–428.
   Google Scholar
• METZLER M, SCHUSTER DP & THE PHASE II PAFASE ARDS PREVENTION GROUP: Recombinant platelet activating factor acetylhydrolase (rPAF-AH) improves organ dysfunction and survival in patients with severe sepsis. Grit. Care Med. (1999) 29:A19 (Abstract).
   Google Scholar
• MCGILL SN, AHMED NA, HU F et al.:Shedding of L-selectin as a mechanism for reduced polymorphonuclear neutrophil exudation in patients with the systemic inflammatory response syndrome. Arch. Surg. (1996) 131:1141–1147.
   PubMed Web of Science ®Google Scholar
• MAEKAWA K, FUTAMI S, NISHIDA M et al.: Effects of trauma and sepsis on soluble L-selectin and cell surface expression of L-selectin and CD1 lb. j Trauma (1998) 44:460–468.
   PubMed Web of Science ®Google Scholar
• STEEBER DA, TANG ML, GREEN NE, ZHANG XO, SLOANE JE, TEDDER TF: Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways. Immune]. (1999) 163(4):2176–2186.
   PubMed Web of Science ®Google Scholar
• RIDINGS PC, BLOOMFIELD GL, HOLLOWAY S et al.: Sepsis-induced acute lung injury is attenuated by selectin blockade following the onset of sepsis. Arch. Surg. (1995) 130(10:1199–1208.
   PubMedGoogle Scholar
• SCHLAG G, REDL HR, TILL GO, DAVIES J, MARTIN, DUMONT L: Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons. Grit. Care Med. (1999) 27(9):1900–1907.
   PubMed Web of Science ®Google Scholar
• CARRAWAY MS, WELTY-WOLF KE, KANTROW SP etal.: Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons. Am. I Respir. Grit. Care Med. (1998) 157(3, Pt 1):938–949.
   Google Scholar
• FERRI LE, SWARTZ D, CHRISTOU NV: Soluble L-selectin at levels present in septic patients diminishes leukocyte-endothelial cell interactions in mice in vivo: a mechanism for decreased leukocyte delivery to remote sites in sepsis. Grit. Care Med. (2001) 29(1):117–122.
   PubMed Web of Science ®Google Scholar
• FERRI LE, PASCUAL J, SEELY AJ, CHAUDHURY P, CHRISTOU NV: Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis. Grit. Care Med. (2002) 30(8):1842–1847.
   PubMed Web of Science ®Google Scholar
• WANG H, BLOOM O, ZHANG M et al.: HMG-1 as a late mediator of endotoxin lethality in mice. Science (1999) 285(5425):248–251.
   PubMed Web of Science ®Google Scholar
• WANG H, YANG H, CZURA CJ, SAMA AE, TRACEY KJ: HMGB1 as a late mediator of lethal systemic inflammation. Am. J. Respir. Grit. Care Med. (2001) 164(10, Pt 1):1768–1773.
   Google Scholar
• LEHMANN LE, NOVENDER U, SCHROEDER S et al.: Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med. (2001) 27(8):1412–1415.
   PubMed Web of Science ®Google Scholar
• CALANDRA T, ECHTENACHER B, ROY DL et al.: Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat. Med. (2000) 6(2):164–170.
   PubMed Web of Science ®Google Scholar
• INTHORN D, HOFFMAN JN, HARTL WH, MUHLBAYER D, JOCHUM M: Effect of antithrombin III Suppl.ation on inflammatory response in patients with severe sepsis. Shock (1998) 10(2):90–96.
   Google Scholar
• EISELE B, LAMY M, THUS LG etal.: Antithrombin III in patients with severe sepsis: A randomized placebo-controlled double blind multicenter trial plus a meta-analysis on all randomized placebo-controlled multicenter trials with antithrombin III in severe sepsis. Intensive Care Med. (1998) 24:663–672.
   Google Scholar
• BAUDO F, CAIMI TM, DE CATALDO E et al.: Antithrombin III replacement therapy in patients with sepsis and/or surgical complications: A controlled double-blind randomized multicenter study. Intensive Care Med. (1998) 24:336–342.
   Google Scholar
• 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(15):1869–1878.
   Google Scholar
• DE JONGE E, DEKKERS PE, CREASEY AA et al.: Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood (2000) 95(4):1124–1129.
   PubMed Web of Science ®Google Scholar
• DE JONGE E, DEKKERS PE, CREASY AA: Tissue factor pathway inhibitor does not influence inflammatory pathways uring human endotoxemia.J. Infect. Dis. (2001) 183(12):1815–1818.
   Google Scholar
• ABRAHAM E, REINHART K, SVOBODA P et al: Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study. Crit. Care Med. (2001) 29(11):2081–2089.
   PubMed Web of Science ®Google Scholar
• CHIRON CORPORATION: Chiron announces result of Phase III study of tifacogin in severe sepsis. (21 November 2001) (Press release).
   Google Scholar
• FAUST SN, LEVIN M, HARRISON OB et al: Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N. Eng] J. Med. (2001) 345:408–416.
   PubMed Web of Science ®Google Scholar
• BERNARD GR, VINCENT JL, LATERRE PF et al.: Efficacy and safety of recombinant human activated protein C for severe sepsis. N EngI. j Med. (2001) 344(10):699–709.
   PubMed Web of Science ®Google Scholar
• ••Major international trial demonstratingimproved survival in severe sepsis with recombinant human APC treatment.
   Google Scholar
• SAITO M, ASAKURA H, JOKAJI H et a/. : Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy. Blood Cava Fibnnolysis (1995) 6:60–64.
   Google Scholar
• PEARSON JM, SCHULTZE AE, SCHWARTZ KA, SCOTT MA, DAVIS JM, ROTH RA: The thrombin inhibitor, hirudin, attenuates lipopolysaccharide-induced liver injury in the rat. j Pharmaca Exp. Ther. (1996) 278:378–383.
   PubMed Web of Science ®Google Scholar
• HERMIDA J, MONTES R, PARAMO JA, ROCHA E: Endotoxin-induced disseminated intravascular coagulation in rabbits: effect of recombinant hirudin on hemostatic parameters, fibrin deposits, and mortality. j Lab. OM. Med. (1998) 131:77–83.
   PubMed Web of Science ®Google Scholar
• MUNOZ MC, MONTES R, HERMIDA J, ORBE J, PARAMO JA, ROCHA E: Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br. J Haemata (1999) 105:117–121.
   PubMed Web of Science ®Google Scholar
• PERNERSTORFER T, HOLLENSTEIN U, HANSEN JB: Lepirudin blunts endotoxin-induced coagulation activation. Blood (2000) 95(5):1729–1734.
   PubMed Web of Science ®Google Scholar
• ERIKSSON M, LARSSON A, SALDEEN T, MATTSSON C: Melagatran, a low molecular weight thrombin inhibitor, counteracts endotoxin-induced haemodynamic and renal dysfunctions in the pig. Thromb. Haemost. (1998) 80(6):1022–1026.
   PubMed Web of Science ®Google Scholar
• ERIKSSON M, SALDEEN T, MATTSSON C, LARSSON A: Effects of melagatran, an inhibitor of thrombin, on fibrin deposits, haemodynamics, and platelet count in endotoxaemic pigs. Acta Anaesthesia Scala. (2000) 44(1):24–31.
   PubMed Web of Science ®Google Scholar
• PRESNEILL JJ, WARING PM, LAYTON JE: Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality. Grit. Care Med. (2000) 28(7):2344–2354.
   PubMed Web of Science ®Google Scholar
• HEARD SO, FINK MP, GAMELLI RL etal.: Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the incidence of nosocomial infections in patients with acute traumatic brain injury or cerebral hemorrhage. Grit. Care Med. (1998) 26(4):748–754.
   Google Scholar
• NELSON S, HEYDER AM, STONE J etal.: A randomized controlled trial of Filgrastim for the treatment of hospitalized patients with multilobar pneumonia. Infect. Dis. (2000) 182:970–973.
   Google Scholar
• WUNDERINK RG, LEEPER KV, SCHEIN R et al: Filgrastim in patients with pneumonia and severe sepsis or septic shock. Chest (2001) 119(2):523–529.
   PubMed Web of Science ®Google Scholar
• LAMARI E ANASTASSIOU ED, TSEGENIDIS T, DIMITRACOPOULOS G, KARAMANOS NK: An enzyme immunoassay to determine the levels of specific antibodies toward bacterial surface antigens in human immunoglobulin preparations and blood serum. j Pharm. Biomed. Arial (1999) 20(6):913–920.
   PubMed Web of Science ®Google Scholar
• TRAUTMANN M, HELD TK, SUSA M etal.: Bacterial lipopolysaccharide (LPS)-specific antibodies in commercial human immunoglobulin preparations: superior antibody content of an IgM-enriched product. OM. Exp. Immuria (1998) 111(1):81–90.
   Google Scholar
• ALEJANDRIA MM, LANSANG MA, DANS LF et al.: Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst. Rev (2002) 1:CD001090.
   Google Scholar
• TUGRUL S, OZCAN PE, AKINCI 0 etal.: The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [I5RCTN28863830]. Crit. Care (2002) 6:357–362.
   Google Scholar
• GIAMARELLOS-BOURBOULIS EJ, MEGA A, GRECKA P et al: Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient. Intensive Care Med. (2002) 28:1351–1356.
   PubMed Web of Science ®Google Scholar
• KAUL R, MCGEER A, NORRBY-TEGLUND A et al: Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome-a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect. Dis. (1999) 28(4):800–807.
   PubMed Web of Science ®Google Scholar
• GROVER R, LOPEZ A, LARENTE J et al: Multi-center, randomized, placebo-controlled, double blind study of the nitric oxide-synthase inhibitor 546C88: Effect on survival in patients with septic shock. Crit. Care Med. (1999) 27(Suppl.):A33 (Abstract).
   Google Scholar
• THIEMERMANN C, RUETTEN H, WU C et al: The multiple organ dysfunction syndrome caused by endotoxin in the rat: Attenuation of liver dysfunction by inhibitors of nitric oxide synthase. Br j Pharmacol (1995) 116:2845–2851.
   PubMed Web of Science ®Google Scholar
• FATEHI-HASSANABAD Z, BURNS H, AUGHEY E et al.: Effects of L-canavanine, an inhibitor of inducible nitric oxide synthase, on endotoxin mediated shock in rats. Am. J Physia (1996) 6:194–200.
   Google Scholar
• BUNE A, BRAND M, HEALES S, SHERGILL J, CAMMACK R, COOK H: Inhibition of tetrahydrobiopterin synthesis reduces in vitro nitric oxide production in experimental endotoxic shock. Biochem. Biophys. Res. Comm. (1996) 220(1):13–19.
   PubMed Web of Science ®Google Scholar
• SZABO A, HAKE P, SALZMAN AL, SZABO C: Beneficial effects of mercaptoethylguanidine, an inhibitor of the inducible isoform of nitric oxide synthase and a scavenger of peroxynitrite, in a porcine model of delayed hemorrhagic shock. Crit. Care Med. (1999) 27(7):1343–1350.
   PubMed Web of Science ®Google Scholar
• MIKAWA K, KODAMA SI, NISHINA K, OBARA H: ONO-1714, a new inducible nitric oxide synthase inhibitor, attenuates diaphragmatic dysfunction associated with cerulein-induced pancreatitis in rats. Grit. Care Med. (2001) 29(6):1215–1221.
   PubMed Web of Science ®Google Scholar
• MENEZES JM, HIERHOLZER C, WATKINS SC, BILLIAR TR, PEITZMAN AB, HARBRECHT BG: The modulation of hepatic injury and heat shock expression by inhibition of inducible nitric oxide synthase after hemorrhagic shock. Shock (2002) 17(1):13–18.
   PubMed Web of Science ®Google Scholar
• REAH G, BODENHAM AR, MALLICK A, DAILY EK, PRZYBELSKI RJ: Initial evaluation of diaspirin cross-linked hemoglobin (DCLHb) as a vasopressor in critically ill patients. Grit. Care Med. (1997) 25(9):1480–1488.
   PubMed Web of Science ®Google Scholar
• SLOAN EP, KOENIGSBERG M, GENS D et al.: Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: a randomized controlled efficacy trial. JAMA (1999) 282(19):1857–1864.
   PubMed Web of Science ®Google Scholar
• BONE HG, FISCHER SR, SCHENARTS PJ, MCGUIRE R, TRABER LD, TRABER DL: Continuous infusion of pyridoxalated hemoglobin polyoxyethylene conjugate in hyperdynamic septic sheep. Shock (1998) 10(1):69–76.
   PubMed Web of Science ®Google Scholar
• MENEZES J, HIERHOLZER C, WATKINS SC et al: A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock. Am. J. Physiol (1999) 277(1, Pt 1):G144–G151.
   Google Scholar
• NADLER EP, DICKINSON EC, BEER-STOLZ D et al.: Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. Am. I Physiol Castrointest. Liver Physiol (2001) 281(1):G173–G181.
   PubMed Web of Science ®Google Scholar
• HOTCHKISS RS, SWANSON PE, REEMAN BD et al.: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Grit. Care Med. (1999) 27(7):1230–1251.
   PubMed Web of Science ®Google Scholar
• TINSLEY KW, CHENG SL, BUCHMAN TG et al: Caspases -2, -3, -6, and -9, but not caspase- I, are activated in sepsis-induced thymocyte apoptosis. Shock (2000) 13(1):1–7.
   PubMed Web of Science ®Google Scholar
• HOTCHKISS RS, SWANSON PE, KNUDSON CM et al.: Overexpression of Bc1-2 in transgenic mice decreases apoptosis and improves survival in sepsis. j Immurrol (1999) 162(7):4148–4156.
   Web of Science ®Google Scholar
• BRAUN JS, NOVAK R, HERZOG KH, BODNER SM, CLEVELAND JL, TUOMANEN El: Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat. Med. (1999) 5(3):298–302.
   PubMed Web of Science ®Google Scholar
• FAUVEL H, MARCHETTI E CHOPIN C, FORMSTECHER P, NEVIERE R: Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis. Am. j Physiol Heart Circ. Physiol. (2001) 280(4):H1608–H1614.
   PubMed Web of Science ®Google Scholar
• NEVIERE R, FAUVEL H, CHOPIN C, FORMSTECHER P, MARCHETTI P: Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis. Am. j Respir. Grit. Care Med. (2001) 163(1):218–225.
   PubMed Web of Science ®Google Scholar
• HOTCHKISS RS, CHANG KC, SWANSON PE et al.: Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat. Immurrol (2000) 1(6):496–501.
   PubMed Web of Science ®Google Scholar
• SZABO A, SALZMAN AL, SZABO C: Poly (ADP-ribose) synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. Life ScL (1998) 63(23):2133–2139.
   PubMed Web of Science ®Google Scholar
• SZABO C, CUZZOCREA S, ZINGARELLI B, O'CONNOR M, SALZMAN AL: Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. I Clin. Invest. (1997) 100(3):723–735.
   Google Scholar
• CUZZOCREA S, ZINGARELLI B, COSTANTINO G, SOTTILE A, TETI D, CAPUTI AP: Protective effect of poly(ADP-ribose) synthetase inhibition on multiple organ failure after zymosan-induced peritonitis in the rat. Grit. Care Med. (1999) 27(8):1517–1523.
   PubMed Web of Science ®Google Scholar
• SZABO C, ZINGARELLI B, SALZMAN AL: Protective effect of poly(ADP-ribose) synthetase inhibition on multiple organ failure after zymosan-induced peritonitis in the rat. Grit. Care Med. (1999) 27(8):1517–1523.
   PubMed Web of Science ®Google Scholar
• BAECHTOLD F, SCOTT JA, MARKERT M etal.: Does the activation of poly (ADP-ribose) synthetase mediate tissue injury in the sepsis induced by cecal ligation and puncture? Shock (2001) 16(2):137–142.
   Google Scholar
• THEISEN M, TRAGER K, TUGTEKIN I et al: Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver 02 exchange and energy metabolism during hyperdynamic porcine endotoxemia. Intensive Care Med. (2001) 27(3):586–592.
   PubMed Web of Science ®Google Scholar
• GOLDFARB RD, MARTON A, SZABO E et al: Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis. Grit Cam Med. (2002) 30(5):974–980.
   PubMed Web of Science ®Google Scholar
• LANDRY DW, LEVIN HR, GALLANT EM et al.: Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation (1997) 95(5):1122–1125.
   PubMed Web of Science ®Google Scholar
• SHARSHAR T, CARLIER R, BLANCHARD A et al.: Depletion of neurohypophyseal content of vasopressin in septic shock. Grit. Care Med. (2002) 30(3):497–500.
   PubMed Web of Science ®Google Scholar
• LANDRY DW, LEVIN HR, GALLANT EM et al: Vasopressin pressor hypersensitivity in vasodilatory septic shock. Grit. Care Med. (1997) 25(8):1279–1282.
   PubMed Web of Science ®Google Scholar
• LANDRY DW, LEVIN HR, GALLANT EM et al.: Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation (1997) 95(5):1122–1125.
   PubMed Web of Science ®Google Scholar
• TSUNEYOSHI I, YAMADA H, KAKIHANA Y, NAKAMURA M, NAKANO Y, BOYLE WA 3rd: Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Grit. Care Med. (2001) 29(3):487–493.
   PubMed Web of Science ®Google Scholar
• DUNSER MW, MAYR AJ, ULMER H etal.: The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis. Arresth. Arralg. (2001) 93(1):7–13.
   Google Scholar
• MALAY MB, ASHTON RC Jr, LANDRY DW, TOWNSEND RN: Low-dose vasopressin in the treatment of vasodilatory septic shock. j Trauma (1999) 47(4):699–703.
   PubMed Web of Science ®Google Scholar
• PATEL BM, CHITTOCK DR, RUSSELL JA, WALLEY KR: Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology (2002) 96(3):576–582.
   PubMed Web of Science ®Google Scholar
• O'BRIEN A, CLAPP L, SINGER M: Terlipressin for norepinephrine-resistant septic shock. Lancet (2002) 359:1209–1210.
   PubMed Web of Science ®Google Scholar
• LEFERING R, NEUGEBAUSER EA: Steroid controversy in sepsis and septic shock: a meta-analysis. Grit Care Med. (1995) 23(7):1294–1303.
   PubMed Web of Science ®Google Scholar
• CRONIN L, COOK DJ, CARLET J etal.: Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Grit. Care Med. (1995) 23(8):1430–1439.
   Google Scholar
• DE GANS J, VAN DE BEEK D: Dexamethasone in adults with bacterial meningitis. N Engl. I Med. (2002) 347(20):1549–1556.
   PubMed Web of Science ®Google Scholar
• •RCT demonstrating that treatment with dexamethasone in adults with acute bacterial meningitis is associated with mortality reduction.
   Google Scholar
• ANNANE D, BELLISSANT E, SEBILLE V et al.: Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal reserve. Br. J. Clin. Pharmacy]. (1998) 46(6):589–597.
   PubMed Web of Science ®Google Scholar
• BELLISSANT E, ANNANE D: Effect of hydrocortisone on phenylephrine-mean arterial pressuredose-response relationship in septic shock. Clin. Pharmacy] Ther. (2000) 68:293–303.
   PubMed Web of Science ®Google Scholar
• BOLLAERT PE, CHARPENTIER C, LEVY B, DEBOUVERIE M, AUDIBERT G, LARCAN A: Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Grit. Care Med. (1998) 26:645–650.
   PubMed Web of Science ®Google Scholar
• BRIEGEL J, FORST H, HALLER M et al.: Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Grit. Care Med. (1999) 27(4):723–732.
   PubMed Web of Science ®Google Scholar
• KEY D: Effects of hydrocortisone on the immune response in patients with septic shock: results from a double-blind cross-over study. J. Arias& likens. (1999) 1:S195–S196.
   Google Scholar
• CHAWLA K, KUPFER Y, TESSLER S: Hydrocortisone reverses refractory septic shock. Grit. Care Med. (1999) 27:A33.
   Web of Science ®Google Scholar
• 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(7):862–871.
   PubMed Web of Science ®Google Scholar
• ••This study demonstrates that abnormaladrenal function is common in patients with septic shock, and that corticosteroid supplementation can improve survival in such patients.
   Google Scholar
• EICHACKER PQ, PARENT C, KAHIL A et al.: Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am. J. Respir: Crit. Care Med. (2002) 166 (9) :1197–1205.
   PubMed Web of Science ®Google Scholar
• •The authors use meta-regression analysis to investigate whether a relationship between risk of death and treatment effect explains the disparity between the results of preclinical and clinical trials of anti-inflammatory agents in sepsis.
   Google Scholar