ARDS: ACURASYS (ARDS et Curarisation Systematique)

Question 1

ACURASYS Clinical Questions

Answer 1

Does administration of cisatracurium improve survival when compared to placebo in ICU patients undergoing mechanical ventilation for early severe ARDS?

Question 2

ACURASYS Bottom Line

Answer 2

Paralysis with cisatracurium for 48 hours in patients with early severe ARDS improves 90 day survival and increases ventilator-free days.

Question 3

ACURASYS Primary Outcome

Answer 3

Mortality before discharge or 90 days

Question 4

ACURASYS Inclusion criteria

Answer 4

• Acute respiratory failure and intubated with all of the following for <48h:
  
  • PaO2:FiO2 <150 PEEP of 5 cm H2O or greater TV of 6-8 ml/kg predicted body weight
  • Bilateral pulmonary infiltrates consistent with edema
  • Absence of left atrial hypertension determined by:
    
    • PCWP <18 mmHg Echocardiography if no PCWP
    • and h/o ischemic heart disease or had crackles on auscultation.

Question 5

ACURASYS Intervention

Answer 5

• Patients were sedated to a Ramsay sedation score of 6 then were infused the study drug Cisatracurium - 15 mg IV once then 37.5 mg/hr for 48 hours Placebo
  
  • peripheral nerve stimulators were disallowed
  • Ventilators placed on assist control (AC) with VT of 6-8 mL/kg with modification of FIO2 and PEEP to reach goal SpO2 88-92% or PaO255-80 mmHg
  • An open-label injection of up to two administrations cisatracurium 20 mg IV were allowed in all patients if the end-inspiratory plateau pressure remained ≥32 cm H2O for ≥10 minutes with increasing sedation and decreasing VT and PEEP

Question 6

ACURASYS Criticisms

Answer 6

1. Outcome may not apply to other neuromuscular blocking agents
2. Unknown if later initiation of cisatracurium provides benefit
3. Unknown if conditions affecting neuromuscular blockade would contribute
4. Lower-than-expected mortality rate means that the study was underpowered
5. True blinding is unlikely since unparalyzed patients will trigger a breath on a ventilator
6. Management of ventilator dyssynchrony was not addressed and may have contributed to poor outcomes in the placebo group
7. Efficacy of paralysis was not studied with a train-of-four stimulation and, therefore, effective paralysis cannot be confirmed ICU paresis was not tested a week after awakening per the original publications on this topic had described
8. Unclear if paralysis or another effect (i.e. anti-inflammatory) accounts for the mortality benefit