"Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome".The New England Journal of Medicine. 2019. 380(21):1997-2008.PubMed•Full text•PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does the addition of early continuous neuromuscular blockade with concomitant deep sedation reduce in-hospital mortality at 90 days compared with usual care with lighter sedation targets in patients with moderate-to-severe acute respiratory distress syndrome (ARDS)?

Bottom Line

Among patients with moderate-to-severe ARDS, the addition of early continuous neuromuscular blockade with concomitant deep sedation did not result in a significant difference in mortality at 90 days compared to usual care with lighter sedation targets.

Major Points

Guidelines

Design

- Multicenter, randomized, unblinded clinical trial
- N=1,006 patients with moderate-to-severe ARDS
- Intervention group received 48-hour continuous infusion of cisatracurium with concomitant deep sedation
- Control group received usual care without routine neuromuscular blockade and lighter sedation targets
- Primary outcome: In-hospital mortality at 90 days
- Trial was stopped early for futility based on the second interim analysis

Population

- Inclusion Criteria: Patients under mechanical ventilation for less than 48 hours for moderate-to-severe ARDS
- Exclusion Criteria: Various, including cardiac failure or fluid overload as the primary cause of respiratory failure; see full list in the Supplementary Appendix of the original study
- Baseline Characteristics: Similar in both groups

Interventions

- Intervention group: 48-hour continuous infusion of cisatracurium with deep sedation
- Control group: Standard care including lighter sedation targets
- Same ventilation strategies, including high PEEP, used in both groups

Outcomes

- Primary Outcome: In-hospital death from any cause at 90 days. 42.5% in the intervention group and 42.8% in the control group (between-group difference, −0.3 percentage points; 95% CI, −6.4 to 5.9; P=0.93)
- Secondary Outcomes: Similar between groups in terms of days free of organ dysfunction, days not in ICU, days free of mechanical ventilation, and days not hospitalized at day 28.

Criticisms

- Early exclusion of eligible patients who had previously received neuromuscular blockade could have affected results.
- Treatment was not blinded, potentially influencing assessments of muscle strength and the level of physical activity.
- Possible underuse of prone positioning, which has been shown to reduce mortality in ARDS, might have influenced results.

Funding

- Supported by grants from the National Heart, Lung, and Blood Institute.

Further Reading

- Full NEJM article and supplementary material at NEJM.org.