Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
09 02 2023
09 02 2023
Historique:
pubmed:
24
1
2023
medline:
16
2
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).
Sections du résumé
BACKGROUND
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.
METHODS
In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed.
RESULTS
A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups.
CONCLUSIONS
Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).
Identifiants
pubmed: 36688507
doi: 10.1056/NEJMoa2212663
pmc: PMC10685906
mid: NIHMS1877106
doi:
Substances chimiques
Vasoconstrictor Agents
0
Banques de données
ClinicalTrials.gov
['NCT03434028']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-510Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL123018
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123031
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123020
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122989
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123004
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123008
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123022
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123023
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123027
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123009
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122989, U01 HL122998, U01 HL123004, U01 HL12
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122998
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123033
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123010
Pays : United States
Investigateurs
Jay S Steingrub
(JS)
Howard Smithline
(H)
Mark Tidswell
(M)
Lori Kozikowski
(L)
Sherell Thornton-Thompson
(S)
Lesley De Souza
(L)
Cynthia Kardos
(C)
Sarah Romain
(S)
Scott Oullette
(S)
Peter Hou
(P)
Rebecca M Baron
(RM)
Anthony F Massaro
(AF)
Imoigele P Aisiku
(IP)
Raghu R Seethala
(RR)
Lauren N Precopio
(LN)
Torben K Becker
(TK)
Christa M Campbell
(CM)
Elida Benitez
(E)
Marie-Carmelle Elie
(MC)
Matthew Shaw
(M)
Tori X Tran
(TX)
Charles R Wira
(CR)
Carolyn Brokowski
(C)
Jonathan M Siner
(JM)
Justin B Belsky
(JB)
Lauren E Ferrante
(LE)
John E Sather
(JE)
Ani Aydin
(A)
Nathan I Shapiro
(NI)
Daniel Talmor
(D)
Valerie Banner-Goodspeed
(V)
Thomas O'Mara
(T)
Charlotte Kirk
(C)
Kelly Harrison
(K)
Lisa Kurt
(L)
Margaret Schermerhorn
(M)
Katherine Boyle
(K)
Nicole Dubosh
(N)
Sharon Hayes
(S)
Eric Hyder
(E)
David Chiu
(D)
Oren Mechanic
(O)
Ted Raddell
(T)
Lihini Keenawinna
(L)
Kostas Andreo
(K)
Michael R Filbin
(MR)
Kathryn Hibbert
(K)
Blair Alden Parry
(BA)
Kendall Lavin-Parsons
(K)
Natalie Pulido
(N)
Alan E Jones
(AE)
James Galbraith
(J)
Rebekah Peacock
(R)
Utsav Nandi
(U)
Michael A Puskarich
(MA)
Matthew E Prekker
(ME)
Audrey Hendrickson
(A)
Jamie Stang
(J)
Paige DeVries
(P)
David Miru
(D)
Andre de Souza Licht
(A)
Pam Sigel
(P)
Patricia Arsenault
(P)
Ronald A Reilkoff
(RA)
Eric Jaton
(E)
Abbey Staugaitis
(A)
Michael Matthay
(M)
Kimberly Yee
(K)
Kimia Ashktorab
(K)
Anika Agrawal
(A)
Rachel Gropper
(R)
Steven Y Chang
(SY)
Gregory W Hendey
(GW)
George Lim
(G)
Nida Qadir
(N)
Andrea Tam
(A)
Rebecca Beutler
(R)
Joseph E Levitt
(JE)
Jenny G Wilson
(JG)
Angela J Rogers
(AJ)
Rosemary Vojnik
(R)
Jonasel Roque
(J)
Timothy E Albertson
(TE)
James A Chenoweth
(JA)
Christian Sandrock
(C)
Skyler J Pearson
(SJ)
Erin Hardy
(E)
Alyssa Hughes
(A)
Kyndra Sousa
(K)
Kinsley Hubel
(K)
Eyad Almasri
(E)
Elizabeth Vidales
(E)
Bela Patel
(B)
Ryan Huebinger
(R)
Adit A Ginde
(AA)
Marc Moss
(M)
Neil Aggarwal
(N)
Jeffrey McKeehan
(J)
Lani Finck
(L)
Carrie Higgins
(C)
Michelle Howell
(M)
Ivor S Douglas
(IS)
Jason Haukoos
(J)
Stacy Trent
(S)
Terra Hiller
(T)
Carolynn Lyle
(C)
Ana Garcia
(A)
Stephanie Gravitz
(S)
Ivan N Co
(IN)
Pauline K Park
(PK)
Robert Hyzy
(R)
Kristine Nelson
(K)
J Victor Jimenez
(JV)
Christopher M-C Fung
(CM)
Jakob I McSparron
(JI)
Norman Olbrich
(N)
Sinan Hanna
(S)
Mark Williams
(M)
Raj Kapoor
(R)
Jean Nash
(J)
Meghan Willig
(M)
Robert Sherwin
(R)
Robert Ehrman
(R)
James Paxton
(J)
John Wilburn
(J)
Michelle Ng Gong
(M)
Ari Moskowitz
(A)
Rahul Nair
(R)
William Nkemdirim
(W)
Hiwet Tzehaie
(H)
Jen-Ting Chen
(JT)
Amira Mohamed
(A)
Brenda Lopez
(B)
Sabah Boujid
(S)
Manuel Hache Marliere
(M)
Lynne D Richardson
(LD)
Kusum Mathews
(K)
Patrick Maher
(P)
Samuel Acquah
(S)
Neha Goel
(N)
Jarrod M Mosier
(JM)
Cameron Hypes
(C)
Bhupinder Natt
(B)
Bryan A Borg
(BA)
Elizabeth Salvagio Campbell
(E)
Kristin M Hudock
(KM)
Opeolu Adeoye
(O)
R Duncan Hite
(RD)
Evan L Ramser
(EL)
Michael Hellman
(M)
Autumn Cresie
(A)
Sara Keegan
(S)
Abhijit Duggal
(A)
Siddharth Dugar
(S)
Omar Mehkri
(O)
Andrei Hastings
(A)
Kiran Ashok
(K)
Stephanie Stoianoff
(S)
Matthew C Exline
(MC)
Jason J Bischof
(JJ)
Thomas E Terndrup
(TE)
Henry E Wang
(HE)
Joshua A Englert
(JA)
Jennifer A Frey
(JA)
Sarah C Karow
(SC)
D Mark Courtney
(DM)
Richard Wunderink
(R)
Helen Donnelly
(H)
Megan Rowland
(M)
Kate Piserchia
(K)
Nicholas J Johnson
(NJ)
Bryce R H Robinson
(BRH)
Catherine L Hough
(CL)
Stephanie Gundel
(S)
Sakshi Seghal
(S)
Sarah Katsandres
(S)
Kelsey Jiang
(K)
Sarah Dean
(S)
Megan Fuentes
(M)
Maranda Newton
(M)
Emily Petersen
(E)
Akram Khan
(A)
Olivia Krol
(O)
Milad Karami Jouzestani
(M)
Makrina Kamel
(M)
Ebaad Haq
(E)
Zach Zouyed
(Z)
Peter Chen
(P)
Sam Torbati
(S)
Susan Jackman
(S)
Niree Hindoyan
(N)
Joseph Meza
(J)
Shane O'Mahony
(S)
Julie Wallick
(J)
Alexandra Duven
(A)
Dakota Fletcher
(D)
Alexandra Weissman
(A)
Donald M Yealy
(DM)
Sarah McGarry
(S)
Bryan J McVerry
(BJ)
David T Huang
(DT)
Michael A Turturro
(MA)
Derek C Angus
(DC)
Jordan Schooler
(J)
Lawrence E Kass
(LE)
Nina T Gentile
(NT)
Nathaniel Marchetti
(N)
Hannah Reimer
(H)
D Clark Files
(DC)
Kevin W Gibbs
(KW)
Chadwick Miller
(C)
Mary LaRose
(M)
Lori Flores
(L)
Lauren Koehler
(L)
Peter E Morris
(PE)
Jamie Sturgill
(J)
Ashley Montgomery-Yates
(A)
Evan P Cassity
(EP)
Sanjay Dhar
(S)
Marjolein de Wit
(M)
Jessica Mason
(J)
Aamer Syed
(A)
Andrew J Goodwin
(AJ)
Abbey Grady
(A)
Caitlan Lematty
(C)
Charles Terry
(C)
Cynthia Oliva
(C)
Kyle Enfield
(K)
Mark Sochor
(M)
Mary Marshall
(M)
Miranda West
(M)
Ashley Simpson
(A)
Lindsay M Leither
(LM)
Samuel M Brown
(SM)
Ithan Peltan
(I)
Joseph Bledsoe
(J)
Melissa Fergus
(M)
Valerie Aston
(V)
Quinn Montgomery
(Q)
Rilee Smith
(R)
Katie Brown
(K)
Brent Armbruster
(B)
Darrin Applegate
(D)
Estelle Harris
(E)
Elizabeth A Middleton
(EA)
Robert Paine
(R)
Lindsey J Waddoups
(LJ)
Amber Plante
(A)
Scott Youngquist
(S)
John Eppensteiner
(J)
Andrew Bouffler
(A)
Christopher Cox
(C)
Alexander T Limkakeng
(AT)
Adam Breslin
(A)
Bennett deBoisblanc
(B)
Matthew Lammi
(M)
Kyle Happel
(K)
David Janz
(D)
Paula Lauto
(P)
Connie Romaine
(C)
Marie Childs Sandi
(M)
Wesley H Self
(WH)
Todd W Rice
(TW)
Matthew W Semler
(MW)
Jonathan D Casey
(JD)
Margaret Hays
(M)
Adrienne Baughman
(A)
Shannon Pugh
(S)
Jakea Johnson
(J)
David B Page
(DB)
Derek W Russell
(DW)
Donna S Harris
(DS)
Shannon S Carson
(SS)
Jason Mock
(J)
Eugenia B Quackenbush
(EB)
Colleen Rice
(C)
David A Schoenfeld
(DA)
B Taylor Thompson
(BT)
Douglas L Hayden
(DL)
Nancy Ringwood
(N)
Cathryn Oldmixon
(C)
Christine Ulysse
(C)
Richard Morse
(R)
Ariela Muzikansky
(A)
Laura Fitzgerald
(L)
Samuel Whitaker
(S)
Adrian Lagakos
(A)
Weixing Huang
(W)
Poying Lai
(P)
Haley Morin
(H)
Roy G Brower
(RG)
Lora A Reineck
(LA)
Karen Bienstock
(K)
Ejigayehu Demissie
(E)
Michelle Freemer
(M)
James Kiley
(J)
Lauren Kunz
(L)
Mario Stylianou
(M)
Myron Maclawiw
(M)
Gail Weinmann
(G)
Laurie J Morrison
(LJ)
Daniel Brodie
(D)
Charles B Cairns
(CB)
Mark N Gillespie
(MN)
Richard J Kryscio
(RJ)
Damon Scales
(D)
Polly Parsons
(P)
Jason D Christie
(JD)
Neal Dickert
(N)
Deborah Diercks
(D)
Jesse R Hall
(JR)
Nicholas J Horton
(NJ)
Mitchell Levy
(M)
Mark Siegel
(M)
Ian Stiell
(I)
Laurie S Zoloth
(LS)
Rinaldo Bellomo
(R)
Stephen Macdonald
(S)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.
Références
N Engl J Med. 2001 Nov 8;345(19):1368-77
pubmed: 11794169
JAMA. 2017 Oct 3;318(13):1233-1240
pubmed: 28973227
Crit Care Med. 2011 Feb;39(2):259-65
pubmed: 20975548
Ann Emerg Med. 2018 Oct;72(4):457-466
pubmed: 29753517
World J Emerg Med. 2012;3(3):191-6
pubmed: 25215062
Crit Care Med. 2021 Nov 1;49(11):e1063-e1143
pubmed: 34605781
Crit Care. 2014 Dec 27;18(6):696
pubmed: 25673138
Crit Care. 2020 Jan 28;24(1):25
pubmed: 31992351
Shock. 2015 Jan;43(1):68-73
pubmed: 25247784
Crit Care. 2021 Apr 16;25(1):146
pubmed: 33863361
N Engl J Med. 2022 Jun 30;386(26):2459-2470
pubmed: 35709019
J Crit Care. 2018 Oct;47:70-79
pubmed: 29933169
J Intensive Care. 2018 Aug 13;6:50
pubmed: 30123511
J Intern Med. 2015 Apr;277(4):468-77
pubmed: 24931482
Intensive Care Med. 2016 Dec;42(12):1935-1947
pubmed: 26825952
West J Emerg Med. 2021 Feb 10;22(2):369-378
pubmed: 33856325
N Engl J Med. 2011 Jun 30;364(26):2483-95
pubmed: 21615299
Crit Care Med. 2012 Jun;40(6):1753-60
pubmed: 22610181
Crit Care. 2015 Jun 15;19:251
pubmed: 26073560
Chest. 2020 Oct;158(4):1431-1445
pubmed: 32353418
J Intensive Care Med. 2009 Jan-Feb;24(1):35-46
pubmed: 19103612
Intensive Care Med. 2016 Nov;42(11):1695-1705
pubmed: 27686349
Lancet Respir Med. 2022 Apr;10(4):367-377
pubmed: 35026177
Crit Care. 2010;14(4):R142
pubmed: 20670424
Intensive Care Med. 2015 Sep;41(9):1549-60
pubmed: 25952825
Crit Care. 2015 Jan 08;19:5
pubmed: 25572383
J Hosp Med. 2015 Sep;10(9):581-5
pubmed: 26014852
Crit Care. 2008;12(3):R74
pubmed: 18533029
J Crit Care. 2011 Dec;26(6):613-9
pubmed: 21514094
Crit Care. 2013 Nov 29;17(6):R278
pubmed: 24289206
Ann Intensive Care. 2014 Jun 21;4:21
pubmed: 25110606