Table 1 The top 50 cited clinical trials on sepsis.

1

Bernard GR, Vincent JL, Laterre P, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr: Efficacy and safety of recombinant human activated protein C for severe sepsis. New England Journal of Medicine 2001, 344:699-709.

2932

2

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early Goal-Directed Therapy C: Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine 2001, 345:1368-1377.

2538

3

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. Critical Care Medicine 2001, 29(7):1303-1310.

2158

4

Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. New England Journal of Medicine 2003, 348:1546-1554.

1551

5

Annane D, Sebille V, Charpentier C, Bollaert PE, François B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troché G, Chaumet-Riffaud P, Bellissant E: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA-Journal of the American Medical Association 2002, 288:862-871.

1227

6

Ziegler EJ, Fisher CJ, Sprung CL, Straube RC, Sadoff JC, Foulke GE, Wortel CH, Fink MP, Dellinger RP, Teng NN: Treatment of gram-negative bacteremia and septic shock with HA-1a human monoclonal-antibody against endotoxin - a randomized, double-blind, placebo-controlled trial. New England Journal of Medicine 1991, 324:429-436.

1152

7

Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA: A controlled clinical-trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. New England Journal of Medicine 1987, 317:653-658.

902

8

Rangelfrausto 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-Journal of the American Medical Association 1995, 273:117-123.

827

9

Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. New England Journal of Medicine 2008, 358:125-139.

738

10

Casey LC, Balk RA, Bone RC: Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Annals of Internal Medicine 1993, 119:771-778.

729

11

Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C: High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993, 341:515-518.

693

12

Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, Damske BA, Parrillo JE: Profound but reversible myocardial depression in patients with septic shock. Annals of Internal Medicine 1984, 100:483-490.

655

13

Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA, Kuhl MR, Brown RO: Enteral versus parenteral-feeding - effects on septic morbidity after blunt and penetrating abdominal-trauma. Annals of Surgery 1992, 215:503-513.

650

14

Fisher CJ, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E: Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. New England Journal of Medicine 1996, 334:1697-1702.

649

15

Hack CE, Degroot ER, Feltbersma RJF, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ, Thijs LG, Aarden LA:Increased plasma-levels of interleukin-6 in sepsis. Blood 1989, 74:1704-1710.

643

16

Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine 2006, 34(6):1589-1596.

598

17

Fisher CJ, Dhainaut JFA, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL: Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome - results from a randomized, double-blind, placebo-controlled trial. JAMA-Journal of the American Medical Association 1994, 271(23):1836-1843.

591

18

Greenman RL, Schein RMH, Martin MA, Wenzel RP, MacIntyre NR, Emmanuel G, Chmel H, Kohler RB, McCarthy M, Plouffe J: A controlled clinical-trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA-Journal of the American Medical Association 1991, 266:1097-1102.

564

19

Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Pénzes I, Kübler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM: High-dose a randomized antithrombin III in severe sepsis - A randomized controlled trial. JAMA-Journal of the American Medical Association 2001, 286:1869-1878.

552

20

Docke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W: Monocyte deactivation in septic patients: Restoration by IFN-gamma treatment. Nature Medicine 1997, 3:678-681.

510

21

Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E: Serum cytokine levels in human septic shock - relation to multiple-system organ failure and mortality. Chest 1993, 103:565-575.

506

22

Ochoa JB, Udekwu AO, Billiar TR, Curran RD, Cerra FB, Simmons RL, Peitzman AB: Nitrogen-oxide levels in patients after trauma and during sepsis. Annals of Surgery 1991, 214:621-626.

505

23

Brunbuisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Régnier B: Incidence, risk-factors, and outcome of severe sepsis and septic shock in adults - a multicenter prospective-study in intensive-care units. JAMA-Journal of the American Medical Association 1995, 274:968-974.

498

24

Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R: Efficacy and safety of monoclonal-antibody to human tumor-necrosis-factor-alpha in patients with sepsis syndrome - a randomized, controlled, double-blind, multicenter clinical-trial. JAMA-Journal of the American Medical Association 1995, 273:934-941.

491

25

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK: Late-onset sepsis in very low birth weight neonates: The experience of the NICHD Neonatal Research Network. Pediatrics 2002, 110:285-291.

490

26

Calandra T, Baumgartner JD, Grau GE, Wu MM, Lambert PH, Schellekens J, Verhoef J, Glauser MP: Prognostic values of tumor-necrosis-factor cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Journal of Infectious Diseases 1990, 161:982-987.

473

27

Damas P, Ledoux D, Nys M, Vrindts Y, De Groote D, Franchimont P, Lamy M: Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Annals of Surgery 1992, 215:356-362.

465

28

Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Critical Care Medicine 1999, 27:1230-1251.

463

29

Sprung CL, Caralis PV, Marcial EH, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE: The effects of high-dose corticosteroids in patients with septic shock - a prospective, controlled-study. New England Journal of Medicine 1984, 311:1137-1143.

461

30

Danner RL, Elin RJ, Hosseini JM, Wesley RA, Reilly JM, Parillo JE: Endotoxemia in human septic shock. Chest 1991, 99:169-175.

458

31

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. New England Journal of Medicine 2008, 358:111-124.

458

32

Meakins JL, Pietsch JB, Bubenick O, Kelly R, Rode H, Gordon J, MacLean LD: Delayed-hypersensitivity - indicator of acquired failure of host defenses in sepsis and trauma. Annals of Surgery 1977, 186:241-250.

449

33

Annane D, Sebille V, Troche G, Raphaël JC, Gajdos P, Bellissant E: A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA-Journal of the American Medical Association 2000, 283:1038-1045.

444

34

Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, Dayer JM: High bronchoalveolar levels of tumor-necrosis-factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory-distress syndrome after trauma, shock, or sepsis. American Review of Respiratory Disease 1992, 145:1016-1022.

443

35

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. Critical Care Medicine 1999, 27:723-732.

426

36

Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A: Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Critical Care Medicine 1998, 26:645-650.

425

37

Munoz C, Carlet J, Fitting C, Misset B, Blériot JP, Cavaillon JM: Dysregulation of invitro cytokine production by monocytes during sepsis. Journal of Clinical Investigation 1991, 88:1747-1754.

424

38

Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D: Sepsis in European intensive care units: Results of the SOAP study. Critical Care Medicine 2006, 34:344-353.

415

39

Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P: Septic shock, multiple organ failure, and disseminated intravascular coagulation - compared patterns of antithrombin-III, protein-C, and protein-S deficiencies. Chest 1992, 101:816-823.

414

40

Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, Cheval C, Monchi M, Teboul JL, Riché F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF: Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality - A multicenter study. JAMA-Journal of the American Medical Association 1999, 282:561-568.

412

41

Marik PE, Sibbald WJ: Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA-Journal of the American Medical Association 1993, 269:3024-3029.

411

42

Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P: Effects of a nitric-oxide synthase inhibitor in humans with septic shock. Cardiovascular Research 1994, 28:34-39.

410

43

Clowes GHA, George BC, Villee CA, Saravis CA: Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. New England Journal of Medicine 1983, 308:545-552.

407

44

Abraham E, Laterre P, Garg R, Levy H, Talwar D, Trzaskoma BL, François B, Guy JS, Brückmann M, Rea-Neto A, Rossaint R, Perrotin D, Sablotzki A, Arkins N, Utterback BG, Macias WL: Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. New England Journal of Medicine 2005, 353:1332-1341.

401

45

Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettilä V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA:Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis - A randomized controlled trial. JAMA-Journal of the American Medical Association 2003, 290:238-247.

395

46

Noone P, Parsons TMC, Pattison JR, Slack RC, Garfield-Davies D, Hughes K: Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. British Medical Journal 1974, 1:477-481.

384

47

Landry DW, Levin HR, Gallant EM, Ashton RC Jr, Seo S, D'Alessandro D, Oz MC, Oliver JA: Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997, 95:1122-1125.

383

48

Askanazi J, Carpentier YA, Elwyn DH, Nordenström J, Jeevanandam M, Rosenbaum SH, Gump FE, Kinney JM: Influence of total parenteral-nutrition on fuel utilization in injury and sepsis. Annals of Surgery 1980, 191:40-46.

381

49

Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL: Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. American Journal of Respiratory and Critical Care Medicine 2000, 162:134-138.

372

50

Lorenz E, Mira JP, Frees KL, Schwartz DA: Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Archives of Internal Medicine 2002 , 162 :1028-1032.

372