"Cisatracurium in Early Acute Respiratory Distress Syndrome". The New England Journal of Medicine. 2010. 363(12):1107-1116. 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 Outcomes
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with early, severe ARDS, does administration of neuromuscular blocking agent (cisatracurium) for 48 hours improve clinical outcomes?

Bottom Line

In patients with early, severe ARDS, administration of cisatracurium for 48 hours improved the adjusted 90-day survival rate, increased time off the ventilator without increasing muscle weakness, but did not significantly improve the overall 90-day mortality.

Major Points

Guidelines

Current guidelines suggest that neuromuscular blocking agents are appropriate for facilitating mechanical ventilation in patients with severe ARDS when sedation is inadequate, but the study's findings need further replication and expansion before wider clinical adoption.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial.

Population

A total of 340 patients with severe ARDS.

Inclusion Criteria
- Endotracheal mechanical ventilation for acute hypoxemic respiratory failure
- PaO2:FIO2 less than 150 with ventilator set to deliver a positive end-expiratory pressure of 5 cm H2O or higher and a tidal volume of 6 to 8 ml/kg of predicted body weight.

Exclusion Criteria
- Left atrial hypertension
- Neuromuscular disease
- Pregnant or breastfeeding
- Extreme obesity

Baseline Characteristics
There were no significant differences between the groups except for a lower mean PaO2:FIO2 in the cisatracurium group.

Interventions

Patients were randomized to receive either cisatracurium besylate or placebo for 48 hours.

Outcomes

Primary Outcomes
- 90-day in-hospital mortality rate
- Adjusted hazard ratio for death at 90 days was 0.68 in the cisatracurium group versus placebo.

Secondary Outcomes
- 28-day mortality
- Ventilator-free days
- Days without organ failure
- Rate of barotrauma
- Rate of ICU-acquired paresis
- MRC scores on day 28 and at ICU discharge

Criticisms

- Results are specific to cisatracurium and might not apply to other neuromuscular blocking agents
- The absence of data on conditions that might affect neuromuscular blockade effectiveness
- Underpowered because the observed mortality rate was lower than expected in the placebo group

Funding

Assistance Publique–Hôpitaux de Marseille and a grant from the Ministère de la Santé.

Further Reading

The full list of articles for further reading is available with the full text of this article at NEJM.org.