Early neuromuscular blockade in the acute respiratory distress syndrome

National Heart, Lung, and Blood Institute PETAL Clinical Trials Network

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1997-2008
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number21
DOIs
StatePublished - May 23 2019
Externally publishedYes

Fingerprint

Neuromuscular Blockade
Adult Respiratory Distress Syndrome
Severe Acute Respiratory Syndrome
Positive-Pressure Respiration
Control Groups
Artificial Respiration
Deep Sedation
Medical Futility
Oxygen
Neuromuscular Blocking Agents
Partial Pressure
Random Allocation
Cause of Death
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

National Heart, Lung, and Blood Institute PETAL Clinical Trials Network (2019). Early neuromuscular blockade in the acute respiratory distress syndrome. New England Journal of Medicine, 380(21), 1997-2008. https://doi.org/10.1056/NEJMoa1901686

Early neuromuscular blockade in the acute respiratory distress syndrome. / National Heart, Lung, and Blood Institute PETAL Clinical Trials Network.

In: New England Journal of Medicine, Vol. 380, No. 21, 23.05.2019, p. 1997-2008.

Research output: Contribution to journalArticle

National Heart, Lung, and Blood Institute PETAL Clinical Trials Network 2019, 'Early neuromuscular blockade in the acute respiratory distress syndrome', New England Journal of Medicine, vol. 380, no. 21, pp. 1997-2008. https://doi.org/10.1056/NEJMoa1901686
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early neuromuscular blockade in the acute respiratory distress syndrome. New England Journal of Medicine. 2019 May 23;380(21):1997-2008. https://doi.org/10.1056/NEJMoa1901686
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. / Early neuromuscular blockade in the acute respiratory distress syndrome. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 21. pp. 1997-2008.
@article{3520ec24d62e438b947bb5e3567b8c8d,
title = "Early neuromuscular blockade in the acute respiratory distress syndrome",
abstract = "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.",
author = "{National Heart, Lung, and Blood Institute PETAL Clinical Trials Network} and Marc Moss and Huang, {David T.} and Brower, {Roy G.} and Ferguson, {Niall D.} and Ginde, {Adit A.} and Gong, {Michelle Ng} and Grissom, {Colin K.} and Stephanie Gundel and Douglas Hayden and {Duncan Hite}, R. and Hou, {Peter C.} and Hough, {Catherine L.} and Iwashyna, {Theodore J.} and Akram Khan and Liu, {Kathleen D.} and Daniel Talmor and {Taylor Thompson}, B. and Ulysse, {Christine A.} and Yealy, {Donald M.} and Angus, {Derek C.}",
year = "2019",
month = "5",
day = "23",
doi = "10.1056/NEJMoa1901686",
language = "English (US)",
volume = "380",
pages = "1997--2008",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "21",

}

TY - JOUR

T1 - Early neuromuscular blockade in the acute respiratory distress syndrome

AU - National Heart, Lung, and Blood Institute PETAL Clinical Trials Network

AU - Moss, Marc

AU - Huang, David T.

AU - Brower, Roy G.

AU - Ferguson, Niall D.

AU - Ginde, Adit A.

AU - Gong, Michelle Ng

AU - Grissom, Colin K.

AU - Gundel, Stephanie

AU - Hayden, Douglas

AU - Duncan Hite, R.

AU - Hou, Peter C.

AU - Hough, Catherine L.

AU - Iwashyna, Theodore J.

AU - Khan, Akram

AU - Liu, Kathleen D.

AU - Talmor, Daniel

AU - Taylor Thompson, B.

AU - Ulysse, Christine A.

AU - Yealy, Donald M.

AU - Angus, Derek C.

PY - 2019/5/23

Y1 - 2019/5/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85066092762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066092762&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1901686

DO - 10.1056/NEJMoa1901686

M3 - Article

C2 - 31112383

AN - SCOPUS:85066092762

VL - 380

SP - 1997

EP - 2008

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -