ACURASYS: Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

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Link to Article: https://www.nejm.org/doi/10.1056/NEJMoa1005372?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

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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

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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

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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