ACURASYS: Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

Clinical Question

In patients with moderate-severe ARDS does the early use of a neuromuscular blocking agent improve mortality?

  • Type of Trial: RCT - computer generated - stratified by ICU

  • Blinding: double blinded; computer-generated random-number tables with telephone system to ensure allocation concealment

  • Setting: 20 ICUs in France from March 2006-March 2008

  • Intention to treat analysis: yes

PICO

  • Population:

    • 339 adult patients with moderate/severe ARDS as defined by ET mechanical ventilaton for acute hypoxemic respiratory failure and the presence of all the following within <48h: P/F<150 with PEEP>/=5, tidal volume 6-8cc/kg. Bilateral pulm infiltrates and absence of clinical evidence of left atrial hypertension

      • Excluded if:

        • continuous infusion of neuromuscular blocking agent at enrolment

        • pregnancy

        • raised ICP

        • longterm O2 therapy or home ventilation, severe chronic liver disease

        • bone marrow transplant or chemotherapy induced neutropenia

        • pneumothorax

        • expected duration of mechanical ventilation <48 hours or decision to withhold life sustaining treatment

        • actual body weight >1kg/cm height

  • Intervention:

    • Neuromuscular blocking agent for 48 hours - cisatracurium 15mg bolus followed by infusion of 37.5mg/hr for 48h

  • Control:

    • Placebo. All patients on volume assisted control ventilation, tidal volumes 6-8 cc/kg of predicted body weight, target SpO2 88-95% or PaO2 55-80mmHg, PEEP adjusted acording to ARMA trial

    • llowed two open-label boluses of 20mg cisatracurium  if plateau pressue >32cmH20 despite increasing sedatives and decreasing tidal volume/PEEP

    • Use of peripheral nerve stimulators was not permitted

  • Outcome:

    • Primary outcome: adjusted 90 day mortality significantly lower in cisatracurium group

    • Secondary outcomes:

      • actual 90 day mortality - no significant differences (31.6% in intervention vs 40.7% in control, p=0.08)

    • Comparing cisatracurium group vs. placebo

      • significantly more patients in placebo group had

        • barotrauma

        • pneumothraces

        • received open-label cistracurium in 1st 48 hours following inclusion

      • significantly more patients in cisatracurium group had

        • more days without non-respiratory organ failure

    • No significant difference in incidence of ICU-acquired paresis

  • Sub-group analysis based on PaO2:FiO2 ratio

    • probability of survival to day 90 (log-rank test)

      • PaO2:FiO2 <120, p=0.051

      • PaO2:FiO2 ≥120, p=0.74

Conclusions

In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness

Strengths

  • Randomized controlled trial

  • Double blinded (Clinicians likely to have been able to determine clinically if patient had received neuromuscular blocking agents and therefore may have treated patients differently)

  • Multi-center

  • Protocolised ventilation strategy

Weaknesses

  • With lower than expected mortality the power of the study is much lower than predicted

  • The use of adjusted mortality for primary outcome was not specified when registering the trial on clinical trials

  • 10% of patients excluded due to ‘other reason’

  • Some aspects of management are not comparable to current Piedmont practice (21% swanz-ganz, 30% nitric oxide)

  • Trend towards significant difference in use of corticosteroids

Take Note

  • Further studies to confirm this study would be beneficial - specifically one with standardized protocols for the use of co-interventions such as proning, steroids

  • Overall improves mortality

Sources:

https://www.thebottomline.org.uk

Rachel MulderComment