Trial of early, goal-directed resuscitation for septic shock
Paul R Mouncey, Tiffany M Osborn, G Sarah Power, David A Harrison, M Zia Sadique, Richard D Grieve, Rahi Jahan, Sheila E Harvey, Derek Bell, Julian F Bion, Timothy J Coats, Mervyn Singer, J Duncan Young, Kathryn M Rowan, ProMISe Trial Investigators, Kathryn Rowan, Derek Bell, Julian Bion, Timothy Coats, Richard Grieve, David Harrison, Timothy Hodgetts, Mervyn Singer, Duncan Young, Steve Goodacre, Julian Bion, Caroline Bowers, Phillip Crow, Rupert Pearse, Kathryn Rowan, David Yates, David Bennett, Jon Nicholl, Alasdair Gray, Timothy Walsh, Paul Mouncey, Derek Bell, Julian Bion, Timothy Coats, David Harrison, Sheila Harvey, Rahi Jahan, Tiffany Osborn, Sarah Power, Kathryn Rowan, Mervyn Singer, Jermaine Tan, Duncan Young, Sarah Corlett, Hannah Muskett, Rachael Scott, Vazeer Ahmed, Adrian Boyle, Andy Scott-Donkin, Heather Black, Christopher Smalley, Reni Jacob, Andrea Wooten, Julian Humphrey, Sally Anne Pearson, James Griffiths, Devasena Subramanyam, David Niblett, Sunil Krishnanankutty, Fang Gao-Smith, Teresa Melody, Keith Couper, Raj Nichani, Emma Brennan, Simon Tucker, Jonathan Benger, Judith Edwards, Kathryn Pollock, Dilshan Arawwawala, Alex Hieatt, Fiona McNeela, Derek Bell, Theresa Weldring, Jaime Carungcong, Peter MacNaughton, Helen McMillan, Kate Tantam, Tony Doyle, Sarah Moreton, Stephanie Jones, Jason Kendall, Ruth Worner, Anna Gilbertson, Colin Borland, Suzanne Boys, Shashank Ranjan, Ian Smith, Neil Smith, Victoria Mendham, Paul Smith, Duncan Young, Roser Farras-Araya, David Vallance, Phil Watt, Parizade Raymode, Laszlo Hollos, Phil Hopkins, Paul Riozzi, Harriet Couper, Sinead Helyar, Jonathan Thompson, Dawn Hales, Zubeir Essat, Prem Andreou, Susan Gilby, Phil Chilton, Richard Miller, John Butler, Alison Jefferies, Richard Clark, Graeme Sanders, Nuno Pinto, Catherine Plowright, Richard Innes, Dawn Bayford, Pippa Richards, Shameer Gopal, Jagtar Singh Pooni, Hazel Spencer, James Napier, Ena Warrington, Liam Kevern, Jane Hunt, Colin Barrett, Eliot Sykes, Karen Connelly, Bryan Yates, Coralie Carle, Theresa Croft, Nick Jenkins, Henrik Reschreiter, Julie Camsooksai, Helena Barcraft-Barnes, Catherine Snelson, Colin Bergin, Frank Keats, Vanessa Linnett, Jenny Ritzema, Steve Christian, Daniel Harvey, Philip Miller, Claudia Woodford, Anna Bolland, Liza Keating, David Mossop, Carys Jones, David Martin, Emma Willett, Peter Swallow, Sam McBride, Asim Ijaz, Jay Datta, Jayne Craig, Thomas Owen, Alex Williams, Sean McMullan, Jackie Baldwin, Mehrun Zuleika, Peter Carvalho, Dan Agranoff, Fiona Ingoldby, Laura Ortiz-Ruiz De Gordoa, Carrie Ridley, Ian Clement, Charley Higham, Bruce Martin, Kate Clayton, Julie Chadwick, Christian Frey, Diane Miller, Philippa Laverick, Khurram Iftikhar, David Higgins, Victoria Katsande, Moses Chikungwa, Clare Jackson, Malcolm Watters, Paul Liddiard, Kate Gannon, Richard Howard-Griffin, Stephanie Bell, Heather Blaylock, Isabel Gonzalez, Emmanuel Cirstea, Stephen Bonner, Parvez Moondi, Kate Wong, Joseph Carter, Stephen Hartley, Iain Crossingham, Joanne Hinchcliffe, Leanne Phoenix, Tim Harris, Jason Pott, Geoffrey Bellhouse, Michael Mercer, Pauline Mercer, Hazel Robinson, David Brealey, Jung Ryu, Georgia Becardes, Anne-Marie Morris, Mark Poulson, Loretta Barnett, Ian Massey, Eliot Sykes, Karen Connelly, Bryan Yates, Tim Harris, Imogen Skene, Patrick Nee, Susan Dowling, Amanda McCairn, Roger Duckitt, Richard Venn, Jordi Margalef, Jonathan Redman, Helen Milner, Sara Ma, Paul R Mouncey, Tiffany M Osborn, G Sarah Power, David A Harrison, M Zia Sadique, Richard D Grieve, Rahi Jahan, Sheila E Harvey, Derek Bell, Julian F Bion, Timothy J Coats, Mervyn Singer, J Duncan Young, Kathryn M Rowan, ProMISe Trial Investigators, Kathryn Rowan, Derek Bell, Julian Bion, Timothy Coats, Richard Grieve, David Harrison, Timothy Hodgetts, Mervyn Singer, Duncan Young, Steve Goodacre, Julian Bion, Caroline Bowers, Phillip Crow, Rupert Pearse, Kathryn Rowan, David Yates, David Bennett, Jon Nicholl, Alasdair Gray, Timothy Walsh, Paul Mouncey, Derek Bell, Julian Bion, Timothy Coats, David Harrison, Sheila Harvey, Rahi Jahan, Tiffany Osborn, Sarah Power, Kathryn Rowan, Mervyn Singer, Jermaine Tan, Duncan Young, Sarah Corlett, Hannah Muskett, Rachael Scott, Vazeer Ahmed, Adrian Boyle, Andy Scott-Donkin, Heather Black, Christopher Smalley, Reni Jacob, Andrea Wooten, Julian Humphrey, Sally Anne Pearson, James Griffiths, Devasena Subramanyam, David Niblett, Sunil Krishnanankutty, Fang Gao-Smith, Teresa Melody, Keith Couper, Raj Nichani, Emma Brennan, Simon Tucker, Jonathan Benger, Judith Edwards, Kathryn Pollock, Dilshan Arawwawala, Alex Hieatt, Fiona McNeela, Derek Bell, Theresa Weldring, Jaime Carungcong, Peter MacNaughton, Helen McMillan, Kate Tantam, Tony Doyle, Sarah Moreton, Stephanie Jones, Jason Kendall, Ruth Worner, Anna Gilbertson, Colin Borland, Suzanne Boys, Shashank Ranjan, Ian Smith, Neil Smith, Victoria Mendham, Paul Smith, Duncan Young, Roser Farras-Araya, David Vallance, Phil Watt, Parizade Raymode, Laszlo Hollos, Phil Hopkins, Paul Riozzi, Harriet Couper, Sinead Helyar, Jonathan Thompson, Dawn Hales, Zubeir Essat, Prem Andreou, Susan Gilby, Phil Chilton, Richard Miller, John Butler, Alison Jefferies, Richard Clark, Graeme Sanders, Nuno Pinto, Catherine Plowright, Richard Innes, Dawn Bayford, Pippa Richards, Shameer Gopal, Jagtar Singh Pooni, Hazel Spencer, James Napier, Ena Warrington, Liam Kevern, Jane Hunt, Colin Barrett, Eliot Sykes, Karen Connelly, Bryan Yates, Coralie Carle, Theresa Croft, Nick Jenkins, Henrik Reschreiter, Julie Camsooksai, Helena Barcraft-Barnes, Catherine Snelson, Colin Bergin, Frank Keats, Vanessa Linnett, Jenny Ritzema, Steve Christian, Daniel Harvey, Philip Miller, Claudia Woodford, Anna Bolland, Liza Keating, David Mossop, Carys Jones, David Martin, Emma Willett, Peter Swallow, Sam McBride, Asim Ijaz, Jay Datta, Jayne Craig, Thomas Owen, Alex Williams, Sean McMullan, Jackie Baldwin, Mehrun Zuleika, Peter Carvalho, Dan Agranoff, Fiona Ingoldby, Laura Ortiz-Ruiz De Gordoa, Carrie Ridley, Ian Clement, Charley Higham, Bruce Martin, Kate Clayton, Julie Chadwick, Christian Frey, Diane Miller, Philippa Laverick, Khurram Iftikhar, David Higgins, Victoria Katsande, Moses Chikungwa, Clare Jackson, Malcolm Watters, Paul Liddiard, Kate Gannon, Richard Howard-Griffin, Stephanie Bell, Heather Blaylock, Isabel Gonzalez, Emmanuel Cirstea, Stephen Bonner, Parvez Moondi, Kate Wong, Joseph Carter, Stephen Hartley, Iain Crossingham, Joanne Hinchcliffe, Leanne Phoenix, Tim Harris, Jason Pott, Geoffrey Bellhouse, Michael Mercer, Pauline Mercer, Hazel Robinson, David Brealey, Jung Ryu, Georgia Becardes, Anne-Marie Morris, Mark Poulson, Loretta Barnett, Ian Massey, Eliot Sykes, Karen Connelly, Bryan Yates, Tim Harris, Imogen Skene, Patrick Nee, Susan Dowling, Amanda McCairn, Roger Duckitt, Richard Venn, Jordi Margalef, Jonathan Redman, Helen Milner, Sara Ma
Abstract
Background: Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains.
Methods: We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days.
Results: We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.
Conclusions: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).
Source: PubMed