Paralytics

Clinical Question: Should everyone with COVID-19 requiring mechanical ventilation receive paralysis?

COVID-19 Specific Literature:

• As of March 30, 2020 there is no COVID-19 specific studies evaluating the efficacy of paralytics for COVID-19 ARDS
• Expert Consensus from China published on February 21, 2020 in Zhonghua Jie He He Hu Xi Za Zhi (Chinese Journal of TB and Respiratory Diseases) recommend the use of paralytics only during intubation

Paralytics in ARDS (the evidence):

• The ACURASYS trial published in 2010 showed improved 90 day mortality (OR 0.68, NNT: 7, p = 0.04) in patients with moderate to severe ARDS (P/F ratio < 150) with 48 hour paralysis using cis-atracurium
  • It is important to note this was an adjusted hazard ratio. The actual 90 day mortality did not identify a significant difference with paralysis.
  • Cliff Notes: https://www.thebottomline.org.uk/summaries/icm/acurasys/
  • Full Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa1005372
• Controversy still existed following ACURASYS because the control group in ACURASYS was deeply sedated and the primary endpoint was adjusted. By 2018 no one was still practicing deep sedation in mechanically ventilated patients. So the question was if paralysis (and its requirement for deep sedation) still offered a mortality benefit compared with modern medicine which targets a RASS of -1 to 0 in mechanically ventilated patients.
• The ROSE trial published in 2019 attempted to set the record straight. The ROSE trial was a negative trial and did not identify a significant benefit (p = 0.9) in 90 day mortality for patients with ARDS (P/F < 150) compared with standard of care RASS -1 to 0.
  • Secondary Outcomes:
    • Patients treated with cis-atracurium had a significant increase in cardiovascular events (p = 0.02) compared with the control group
  • Cliff Notes: https://www.thebottomline.org.uk/summaries/icm/rose/
  • Full Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa1901686