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N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.

Goal-directed resuscitation for patients with early septic shock.

Collaborators (257)

Peake S, Delaney A, Bellomo R, Cameron P, Higgins A, Holdgate A, Howe BD, Webb SA, Williams P, Peake S, Delaney A, Bellomo R, Cameron P, Cooper D, Cross A, Gomersall C, Graham C, Higgins AM, Holdgate A, Howe BD, Jacobs I, Johanson S, Jones P, Kruger P, McArthur C, Myburgh J, Nichol A, Pettilä V, Rajbhandari D, Webb SA, Williams A, Williams J, Williams P, Baigent C, Cuthbertson B, Benger J, Emberson J, Bailey M, Bellomo R, Bives G, Cooper D, Higgins A, Howe BD, Jovanovska A, Lam L, Little L, Newby L, Bennett V, Board J, McCracken P, McGloughlin S, Nanjayya V, Teo A, Hill E, Jones P, O'Brien E, Sawtell F, Schimanski K, Wilson D, Bellomo R, Bolch S, Eastwood G, Kerr F, Peak L, Young H, Edington J, Fletcher J, Smith J, Ghelani D, Nand K, Sara T, Cross A, Flemming D, Grummisch M, Purdue A, Fulton E, Grove K, Harney A, Milburn K, Millar R, Mitchell I, Rodgers H, Scanlon S, Coles T, Connor H, Dennett J, Van Berkel A, Barrington-Onslow S, Henderson S, Mehrtens J, Dryburgh J, Tankel A, Braitberg G, O'Bree B, Shepherd K, Vij S, Allsop S, Haji D, Haji K, Vuat J, Bone A, Elderkin T, Orford N, Ragg M, Kelly S, Stewart D, Woodward N, Harjola VP, Okkonen M, Pettilä V, Sutinen S, Wilkman E, Fratzia J, Halkhoree J, Treloar S, Ryan K, Sandford T, Walsham J, Jenkins C, Williamson D, Burrows J, Hawkins D, Tang C, Dimakis A, Holdgate A, Micallef S, Parr M, White H, Morrison L, Sosnowski K, Ramadoss R, Soar N, Wood J, Franks M, Williams A, Hogan C, Song R, Tilsley A, Rainsford D, Soar N, Wells R, Wood J, Dowling J, Galt P, Lamac T, Lightfoot D, Walker C, Braid K, DeVillecourt T, Tan HS, Seppelt I, Chang LF, Cheung WS, Fok SK, Lam PK, Lam SM, So HM, Yan WW, Altea A, Lancashire B, Gomersall CD, Graham CA, Leung P, Arora S, Bass F, Shehabi Y, Isoardi J, Isoardi K, Powrie D, Lawrence S, Ankor A, Chester L, Davies M, O'Connor S, Poole A, Soulsby T, Sundararajan K, Williams J, Greenslade JH, MacIsaac C, Gorman K, Jordan A, Moore L, Ankers S, Bird S, Delaney A, Dowling J, Fogg T, Hickson E, Jewell T, Kyneur K, O'Connor A, Townsend J, Yarad E, Brown S, Chamberlain J, Cooper J, Jenkinson E, McDonald E, Webb S, Buhr H, Coakley J, Cowell J, Hutch D, Gattas D, Keir M, Rajbhandari D, Rees C, Baker S, Roberts B, Farone E, Holmes J, Santamaria J, Winter C, Finckh A, Knowles S, McCabe J, Nair P, Reynolds C, Ahmed B, Barton D, Meaney E, Nichol A, Harris R, Shields L, Thomas K, Karlsson S, Kuitunen A, Kukkurainen A, Tenhunen J, Varila S, Burrows J, Ryan N, Trethewy C, Crosdale J, Smith J, Vellaichamy M, Furyk J, Gordon G, Jones L, Senthuran S, Bates S, Butler J, French C, Tippett A, Kelly J, Kwans J, Murphy M, O'Flynn D, Kurenda C, Otto T, Peake S, Raniga V, Williams P, Ho H, Leung A, Wu H.



Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.


In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.


Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.


In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE number, NCT00975793.).

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