I. Protocolized Standard Care (PSC) Flowchart and Footnotes

SUPPLEMENTARY MATERIALS

I. Protocolized Standard Care (PSC) flowchart and footnotes Footnotes

1. Central line should only be placed and used for venous access. During the 6h ProCESS intervention, CVP and ScvO2 measurements are discouraged. If time-sensitive fluid targets can be achieved with smaller IVs

(e.g., one 18g and one 20g), that is acceptable.

2. Only isotonic fluid should be used (e.g., saline, lactated Ringer’s). Colloids are neither encouraged nor excluded.

3. Fluid replete/overload is defined here as a clinical diagnosis by the treating ProCESS Investigator. Signs and symptoms of overload include, but are not limited to, jugular venous distention, rales, and decreased pulse oximetry readings. Discontinue all IVF (boluses, background rate) once this occurs, until no longer deemed fluid replete/overload.

4. If patient’s SBP is within 10% of known baseline SBP, AND patient is not deemed to be clinically hypoperfused, the SBP>100 mmHg target can be deemed fulfilled. Arterial lines allowed if deemed necessary, but not mandatory. Shock index = heart rate / systolic blood pressure.

5. Hypoperfusion is defined here as a clinical diagnosis by the treating ProCESS Investigator. Signs and symptoms include, but are not limited to, MAP < 65 despite SBP > 100, arterial lactate > 4, mottled skin, oliguria, and altered sensorium.

6. Transfuse PRBCs for Hgb < 7.5 g/dL.

7. From time of prompt by protocol (i.e., not from time of physician order, or from when IV bag hung). II. Centers and investigators as of May 2013 (in alphabetical order, for each trial)

ProCESS

Advocate Christ Medical Center, Oak Lawn – E. Kulstad, H. Watts, K. Hesse. Allegheny General Hospital,

Pittsburgh - A. Venkat. Brigham and Women’s Hospital, Boston - P. Hou, A. Massaro, S. Parmar. Duke

University Medical Center, Durham - A. Limkakeng, J. Govert, W. Drake. East Carolina University,

Greenville- T. Delbridge, K. Brewer, A. Mainhart. George Washington University Medical Center,

Washington, D.C. - A. Dorfman, L. Chawla, E. Brasha-Mitchell. Intermountain Medical Center, Murray - C.

Grissom, T. Allen, B Briggs. LAC + USC Medical Center, Los Angeles - H. Belzberg, S. Swadron, J. Zhu.

Louisiana State University Health Sciences Center, Shreveport - T. Arnold, S. Conrad, K. Hutchinson.

Maricopa Medical Center, Phoenix - F. LoVecchio, R. Carlson, M. Mulrow. Massachusetts General Hospital,

Boston - M. Filbin, A. Waxman, B. A. Parry. Methodist Research Institute, Indianapolis - T. Ellender, C. Naum,

C. Lynn. North Shore University Hospital, Manhasset - A. Sama, T. Slesinger, T. Pastrana. Norwalk Hospital,

Norwalk- J. Fine, M. Carius, C. Belden. Penn State Hershey College of Medicine, Hershey - T. Terndrup, M.

Wojnar, S. Nafeei. Stanford University School of Medicine, Stanford - M. Strehlow, R. Pearl, V. Ojha. Summa

Health System, Akron - S. Wilber, B. Martin, J. Skruck. SUNY Downstate Medical Center, Brooklyn - R. Sinert,

S. Malhotra. Tampa General Hospital, Tampa - D. Orban, R. Paula, C. Targal. Temple University Hospital,

Philadelphia - J. Ufberg, J. Travaline, A. Wang. UC Davis Medical Center, Sacramento - E. Panacek, T.

Albertson, L. Jones. University of Alabama at Birmingham, Birmingham - H. Wang, K. Lai. University of

Arkansas for Medical Sciences, J. Palmer. University of Minnesota Medical Center, Fairview - N. Schmiechen,

C. Weinert, S. Nagamatsu. University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh - D.

Yealy, S. Gunn, P. Carey. University of Pittsburgh Medical Center, Shadyside Hospital, Pittsburgh - R. Wadas, V. Okwiya. University of Utah Health Sciences Center, Salt Lake City - E. Kimball, E. Harris, R. Preston.

Vanderbilt University Medical Center, Nashville - W. Self, D. Dubinski. Washington Hospital Center,

Washington, D.C. - M. Goyal, C. Phillips, R. Migues.

(all in Australia unless specified to New Zealand, NZ, Finland, FL, or Hong Kong, HK or Ireland, IRE)

The Alfred Hospital, Melbourne – P. Cameron, D.J. Cooper, V. Bennett. ANZIC-Research Centre – B. Howe, A.

Jovanovska. Auckland City Hospital, Auckland, NZ – P. Jones. F. Sawtell, K. Schimanski. Austin Health,

Melbourne – R. Bellomo, F. Kerr, L.Peak, . Bendigo Hospital, Bendigo- J. Edington, J. Fletcher, J. Smith.

Blacktown Hospital, Blacktown- D. Ghelani, K. Nand, T. Sara. Box Hill Hospital, Melbourne – A. Cross, M.

Grummisch, A. Purdue. Canberra Hospital, Canberra- K. Grove, I. Mitchell, H. Rodgers, E. Fulton. Central

Gippsland Health Service, Sale – J. Dennett, T. Coles, R. Ziffer, Christchurch Hospital, Christchurch, NZ –S.

Barrington-Onslow, S. Henderson, J. Mehrtens. Coffs Harbour Base Hospital, Coffs Harbour – Tankel, A.

Dandenong Hospital, Melbourne –G. Braitberg, B.O’Bree, K. Shepherd, S. Vij. Frankston Hospital, Melbourne –

K. Haji, L. Goh, S. Allsop. Geelong Hospital, Geelong – A. Bone, N. Orford, M. Ragg. Gosford Hospital,

Gossford – S. Kelly, D. Stewart, N. Woodward. Helsinki University Hospital, Helsinki, FL – V. Pettila, S.

Sutinen, M. Abo. Hornsbury Hospital, Hornsbury – J. Fratzia, J. Halkhoree, T. Solano, S. Treloar. Ipswich

Hospital, Ipswich – K. Ryan, T. Sandford, J. Walsham. John Hunter Hospital, Newcastle – C. Jenkins, D.

Williamson. Joondalup Health Campus, Joondalup – S. Brown, D. Hawkins, C. Tang. Liverpool Hospital,

Liverpool – A. Dimakis, A. Holdgate, M. Parr. Logan Hospital, Meadowbrook – H, White, L. Morrison, K.

Sosnowski. Lyell McEwin Hospital, Elizabeth Vale – R. Ramadoss, J. Wood. Manly Hospital, Manly – M.

Franks. Middlemore Hospital, Auckland, NZ – T. Williams, C. Hogan. Modbury Hospital, SA – Wells, R.

Monash Medical Centre, Clayton – P. Galt, D. Lightfoot, T. Lamac. Nepean Hospital, Penrith – K. Braid, T. Clarke, I. Seppelt. Pamela Youde Nethersole Eastern Hospital, Chai Wan, HK – R. Lam, S. Lam, W. Yan. Port

Macquarie Base, Port Macquarie – A. Altea, B. Lancashire. Prince of Wales Hospital, Shatin, HK –C.

Gomersall.C. Graham, P. Leung. Prince of Wales Hospital, Sydney – S. Arora, F. Bass, Y. Shehabi. Princess

Alexandra, Woolloongabba – K. Isoardi, S. Lawrence. Royal Adelaide Hospital, Adelaide – A. Ankor, L.

Chester, S. O’Connor, K. Sundararajan. Royal Brisbane and Women's Hospital, Brisbane – J. Williams, J.

Greenslaid. Royal Melbourne Hospital, Melbourne – C. MacIsaac, A. Jordan, T. Caf. Royal North Shore

Hospital, St Leonards – S. Bird, A. O’Connor, A. Delaney. Royal Perth Hospital, Perth – J. Chamberlain, S.

Webb. Royal Prince Alfred Hospital, Camperdown – H. Buhr, D. Gattas, D. Rajbhandari. Sir Charles Gairdner

Hospital, Nedlands – S. Baker, B. Roberts. St. Vincent’s Hospital, Melbourne – E. Faraone, J. Holmes, C.

Winter. St. Vincent’s Hospital, Sydney – P. Nair, C. Reynolds. St. Vincent’s University Hospital, IRE – Nichol,

A. Sydney Adventist Hospital, Wahroonga – Harris, R. Shields, L. Tampere University Hospital, Tampere, FL

– A. Kuitunen, J. Tenhunen, S. Karlsson, S. Varila. Tamworth Hospital, Tamworth – J. Burrows, N. Ryan, C.

Trethewy. Townsville Hospital, Townsville – G. Gordon, Reeves S. Western Hospital, Footscray – S. Bates, J.

Butler, C. French. Westmead Hospital, Westmead – J. Kwans, M. Murphy, D. O’Flynn. The Queen Elizabeth

Hospital, Woodville South – C. Kurenda, S. Peake, P. Williams. The Queen Elizabeth Hospital, HK – Leung, A.

Ho, Hiu Fai.

ProMISe

Addenbrooke's Hospital, Cambridge – V. Ahmed, A. Boyle, A. Scott-Donkin. Arrowe Park Hospital, Wirral –

H. Black, D. Jenkins, C. Smalley. Barnsley Hospital, Barnsley – J. Humphrey, J. Griffiths, S.A. Pearson.

Bedford Hospital, Bedford – D. Subramanyam, D. Niblett. Birmingham Heartlands Hospital, Birmingham – F.

Gao-Smith, T. Melody, K. Couper. Bristol Royal Infirmary, Bristol – J. Benger, J. Bewley, L. Flintoff. Blackpool

Victoria Hospital, Blackpool – R. Nichani, E. Brennan, H. Kenworthy. Broomfield Hospital, Chelmsford – D.

Arawwawala, C. Mitchell-Inwang, F. McNeela. Chelsea and Westminster Hospital, London – D. Bell, C. Emerson, T. Weldring. Derriford Hospital, Plymouth – P. MacNaughton, A. Kehoe, H. McMillan. Dorset

County Hospital, Dorchester – T. Doyle, S. Moreton. Frenchay Hospital, Bristol – J. Kendall, E. Oldenbourg,

A. Gilbertson. Hinchingbrooke Hospital, Huntingdon – C. Borland, S. Boys. Hull Royal Infirmary, Hull – I.

Smith, N. Smith, P. Williams. John Radcliffe Hospital, Oxford – D. Young, R. Farras Araya. Kettering General

Hospital, Kettering – P. Watt, N. Spencer, P. Raymode. King’s College Hospital, London – P. Hopkins, G.

Parsons, S. Helyar. Leicester Royal Infirmary, Leicester – J. Thompson, T. Coats, D. Hales. Leighton Hospital,

Crewe – S. Gilby, P. Chilton, R. Miller. Manchester Royal Infirmary, Manchester – J. Butler, B. Foex, A. Royle.

Medway Maritime Hospital, Gillingham – G. Sanders, P. Hayden, C.Plowright. Musgrove Park Hospital,

Taunton – R. Innes, D. Bayford, P. Richards. New Cross Hospital, Wolverhampton – S. Gopal, N. Poonit, L.

Phiri. Newham University Hospital, London – J. Napier, E. Warrington. North Devon District Hospital,

Barnstaple – L. Kevern, J. Hunt. North Tyneside General Hospital, North Shields – E. Sykes, J. Dickson, S.

Duffy. Peterborough City Hospital, Peterborough – C. Carlie, T. Croft. Poole Hospital, Poole – N. Jenkins, H.

Reschreiter, J. Camsooksai. Queen Elizabeth Hospital Birmingham, Birmingham – C. Snelson, J. Bion, F. Keats.

Queen Elizabeth Hospital, Gateshead – V. Linnett, S. Christian, J. Ritzema. Queen’s Medical Centre,

Nottingham – A. Jabbar, P. Miller, R. Ravenscroft. Royal Berkshire Hospital, Reading – L. Keating, D. Mossop,

E. Bowley. Royal Bournemouth Hospital, Bournemouth – D. Martin, P. Swallow, E. Vickers. Royal Lancaster

Infirmary, Lancaster – S. McBride, M. Entwistle, J. Craig. Royal Preston Hospital, Preston – T. Owen, J.

Baldwin, S. McMullen. Royal Surrey County Hospital, Guildford – M. Zuleika, P. Carvalho. Royal Sussex

County Hospital, Brighton – D. Agranoff, F. Ingoldby. Royal Victoria Infirmary, Newcastle upon Tyne – I.

Clement, C. Higham. Salford Royal Hospital, Salford – B. Martin, C. Gavin, K. Clayton. South Tyneside

District Hospital, South Shields – C. Frey, A. Kumar, D. Miller. Southend University Hospital, Southend – K.

Iftikhar, D. Higgins, V. Katsande. Stafford Hospital, Stafford – M. Chikungwa, T. Bentley, C. Jackson. The

Ipswich Hospital, Ipswich – R. Howard-Griffin, S. Bell, H. Blaylock. The James Cook University Hospital,

Middlesbrough – I. Gonzalez, P. Dissmann, K. Colling. The Queen Elizabeth Hospital, King's Lynn – J. Carter, P. Moondi, K. Wong. The Royal Blackburn Hospital, Blackburn – S. Hartley, J. Hinchcliffe, L. Phoenix. The

Royal London Hospital, London – T. Harris, J. Pott. Torbay Hospital, Torquay – M. Mercer, P. Mercer.

University College Hospital, London – D. Brealey, M. Singer, JH. Ryu. University Hospital of North

Staffordshire, Stoke-on-Trent – M. Poulson, S. Plant, I. Massey. Wansbeck General Hospital, Ashington – E.

Sykes, J. Dickson, S. Duffy. Whipps Cross University Hospital, London – Harris. T, I. Skene. Whiston

Hospital, Prescot – P. Nee, S. Dowling, A. McCairn. Worthing Hospital, Worthing – R. Duckitt, R. Venn, J.

Margalef. York Hospital, York – J. Redman, D. Yates, M. Makiela.