Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.
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:
23 05 2019
23 05 2019
Historique:
pubmed:
22
5
2019
medline:
30
5
2019
entrez:
22
5
2019
Statut:
ppublish
Résumé
The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).
Sections du résumé
BACKGROUND
The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.
METHODS
We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days.
RESULTS
The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months.
CONCLUSIONS
Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).
Identifiants
pubmed: 31112383
doi: 10.1056/NEJMoa1901686
pmc: PMC6741345
mid: NIHMS1536873
doi:
Substances chimiques
Neuromuscular Blocking Agents
0
Atracurium
2GQ1IRY63P
cisatracurium
QX62KLI41N
Banques de données
ClinicalTrials.gov
['NCT02509078']
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
1997-2008Subventions
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 : U01HL123031
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122989
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123010
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123027
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123018
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123009
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 HL122998
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123004
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL122989
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123023
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL143053
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123020
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123020
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123009
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL122998
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123022
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123008
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123023
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123022
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01HL123033
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL123027
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)
Mark Tidswell
(M)
Lori Kozikowski
(L)
Leslie De Souza
(L)
Cynthia Kardos
(C)
Peter C Hou
(PC)
Imo P Aisiku
(IP)
Rebecca M Baron
(RM)
Anthony F Massaro
(AF)
Raghu R Seethala
(RR)
Laura E Fredenburgh
(LE)
Zachary A Gandee
(ZA)
Arman Israelyan
(A)
Richard R Riker
(RR)
Adelene Macleaod
(A)
Theresa May
(T)
David Seder
(D)
Thomas E Van der Kloot
(TE)
Nicholas S Hill
(NS)
Veronica Bacong
(V)
Haval Chweich
(H)
Erik Garpestad
(E)
Omar Schweish
(O)
Daniel Talmor
(D)
Nathan Shapiro
(N)
Valerie Banner-Goodspeed
(V)
Sayuri Jinadasa
(S)
Andres Brenes Bastos
(A)
Ednan Bajwa
(E)
Michael R Filbin
(MR)
Kathryn A Hibbert
(KA)
Carrie Holland
(C)
Kelsey Brait
(K)
Patricia A Arsenault
(PA)
Pam Sigel
(P)
Alan E Jones
(AE)
John R Spurzem
(JR)
Michael Puskarich
(M)
Margaret Hope Cruise
(M)
Jasmine J Kolb
(JJ)
Deepti Patki
(D)
Michael A Matthay
(MA)
Kathleen D Liu
(KD)
Carolyn S Calfee
(CS)
Jeffrey E Gotts
(JE)
Brian M Daniel
(BM)
Annika Belzer
(A)
Gregory W Hendey
(GW)
Steven Y Chang
(SY)
Nida Qadir
(N)
Bryan Garber
(B)
Stephanie Guo
(S)
Scott Lewis
(S)
Jamal Sharif
(J)
Joseph Levitt
(J)
Angela Rogers
(A)
Rosemary Vojnik
(R)
Adijat T Asuni
(AT)
Timothy E Albertson
(TE)
Jason Y Adams
(JY)
Maya Juarez
(M)
Brian Morrissey
(B)
Skyler Pearson
(S)
Eyad Almasri
(E)
Janna M Blaauw
(JM)
Alyssa Hughes
(A)
Kyndra Sousa
(K)
Adit Ginde
(A)
Marc Moss
(M)
Lani Finck
(L)
Carrie Higgins
(C)
Jeffrey McKeehan
(J)
Ivor S Douglas
(IS)
Jason Haukoos
(J)
Terra Hiller
(T)
Emily Hopkins
(E)
Judy L Oaks
(JL)
Katie Overdier
(K)
Meggan Schmidt
(M)
David C Van Pelt
(DC)
Jonathan S Tashkin
(JS)
Joan Reischel
(J)
James H Finigan
(JH)
Kenneth Lyn-Kew
(K)
Ryan D Paterson
(RD)
Luciano Lemos-Filho
(L)
Robert C Hyzy
(RC)
Pauline K Park
(PK)
Kristine Nelson
(K)
Ivan N Co
(IN)
Jakob I McSparron
(JI)
Tina Chen
(T)
Sinan Hanna
(S)
Normal Olbrich
(N)
Bruno M DiGiovine
(BM)
Emanuel P Rivers
(EP)
Jackie Day
(J)
Jasreen Gill
(J)
Jayna Gardner Gray
(J)
Gina Hurst
(G)
Namita Jayaprakash
(N)
Anja Kathrina Jaehne
(A)
Sarah Rubino
(S)
Jennifer Swiderek
(J)
Jacqueline Pflaum
(J)
Mark Williams
(M)
Rajat Kapoor
(R)
Tim Ellender
(T)
Daniel Gutteridge
(D)
Jean Nash
(J)
Michelle Ng Gong
(M)
Aluko A Hope
(AA)
Jen-Ting Chen
(JT)
Swarna Gummadi
(S)
Damaris Fuster
(D)
Missiel E Munoz
(ME)
Brenda Lopez
(B)
Lynne D Richardson
(LD)
Sam Acquah
(S)
Kusum Mathews
(K)
Lisa Richman
(L)
Neha N Goel
(NN)
Nan Li
(N)
Gabriel Schneider
(G)
Cindy Clesca
(C)
Natalie S Massenburg
(NS)
R Duncan Hite
(RD)
Abhijit Duggal
(A)
Andrei Hastings
(A)
Omar Mehkri
(O)
Tarik Hanane
(T)
Andrea Rice
(A)
Thomas E Terndrup
(TE)
Matthew C Exline
(MC)
Joshua Englert
(J)
Emily Robart
(E)
Sonal Pannu
(S)
Naeem A Ali
(NA)
Jennifer A Frey
(JA)
Kirk A Stiffler
(KA)
David Norton
(D)
Tammy Roads
(T)
Autumn Studer
(A)
Kristin Hudock
(K)
Derek C Angus
(DC)
Donald M Yealy
(DM)
David T Huang
(DT)
Bryan J McVerry
(BJ)
Denise Scholl
(D)
Caroline Gacka
(C)
Pavan Thangudu
(P)
Rajagopala Padmanabhan
(R)
Vikram Balakumar
(V)
Jennifer G McComb
(JG)
Pam Fazio
(P)
Mary Stefanick
(M)
Chenell L Donadee
(CL)
Matthew Siedsma
(M)
Raghavan Murugan
(R)
Andrew Jockers
(A)
Nancy Campbell
(N)
Allison Muller
(A)
Susan B Promes
(SB)
Catherine Hough
(C)
Bryce R H Robinson
(BRH)
Nicholas J Johnson
(NJ)
Stephanie Gundel
(S)
Sarah C Katsandres
(SC)
Anna M Ungar
(AM)
Jennifer Cardey
(J)
Tzevan Poon
(T)
Sarah Dean
(S)
Steven Haberkorn
(S)
Ebaad Haq
(E)
Bory Kea
(B)
Martin A Schreiber
(MA)
Akram Khan
(A)
Shane D O'Mahony
(SD)
Charlene Boisjolie
(C)
D Clark Files
(DC)
Chadwick D Miller
(CD)
Rita Bakhru
(R)
Lori S Flores
(LS)
Kevin Gibbs
(K)
Mary LaRose
(M)
Lina Purcell
(L)
Patrick E Wright
(PE)
Kyle B Enfield
(KB)
Mark Sochor
(M)
Alexandra Kadl
(A)
Mary Marshall
(M)
Peter E Morris
(PE)
Sanjay Dhar
(S)
Ashley Montgomery-Yates
(A)
Jamie Sturgill
(J)
Sara Pasha
(S)
Marjolein de Wit
(M)
Stella Hamman
(S)
Colin K Grissom
(CK)
Joseph Bledsoe
(J)
Todd Allen
(T)
Naresh Kumar
(N)
Samuel M Brown
(SM)
Mona Hopkins
(M)
Michael Lanspa
(M)
Ithan Peltan
(I)
Ellie Hirshberg
(E)
James Orme
(J)
Mardee Merrill
(M)
Quinn Montgomery
(Q)
Katie Brown
(K)
Brent Armbruster
(B)
Valerie Aston
(V)
Terry Clemmer
(T)
Kira Knight
(K)
Aaron Shepherd
(A)
Corey Sillito
(C)
Barbara Kerwin
(B)
Robert Paine
(R)
Estelle Harris
(E)
Elizabeth Middleton
(E)
Amber Plante
(A)
Dixie Harris
(D)
Wayne Woodward
(W)
David Nielsen
(D)
Todd W Rice
(TW)
Wesley H Self
(WH)
Matthew W Semler
(MW)
Margaret Hayes
(M)
Susan Mogan
(S)
Adrienne Baughman
(A)
David R Janz
(DR)
Paula Lauto
(P)
Margaret M Moore
(MM)
Bennett P deBoisblanc
(BP)
John P Hunt
(JP)
Jennifer L Mooney
(JL)
Sarah E Jolley
(SE)
David A Schoenfeld
(DA)
B Taylor Thompson
(BT)
Kathleen Tiffany Lee
(KT)
Christine Ulysse
(C)
Cathryn F Oldmixon
(CF)
Nancy J Ringwood
(NJ)
Jenna R Pedrin
(JR)
Richard E Morse
(RE)
Douglas Hayden
(D)
Karen Bienstock
(K)
Carol J Blaisdell
(CJ)
Andrea L Harabin
(AL)
Lora A Reineck
(LA)
Peyvand Ghofrani
(P)
Myron A Waclawiw
(MA)
Gail Weinmann
(G)
Laurie J Morrison
(LJ)
Charles B Cairns
(CB)
Shannon Carson
(S)
D Mark Courtney
(DM)
Mark N Gillespie
(MN)
Richard J Kryscio
(RJ)
Polly Parsons
(P)
Jason D Christie
(JD)
Jesse R Hall
(JR)
Nicholas J Horton
(NJ)
Jeffrey A Kline
(JA)
Mitchell Levy
(M)
Mark Siegel
(M)
Ian Stiell
(I)
Laurie S Zoloth
(LS)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
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Informations de copyright
Copyright © 2019 Massachusetts Medical Society.
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