Hyzy Chest Physician 2020 – Editorial on neuromuscular blockade/paralysis and PETAL Network trials

Initial studies into neuromuscular blockade were from Light et al. Anesth Analg 1975;54[2]:219 which showed that could be appealing

Then, showed that NMB could avoid excess tachypnea with increasing oxygenation per Hansen-Flaschen et al. JAMA 1991;26:2870

In ARDSNet, the pts were allowed to breathe up to 35/min

• this prompted the thought that maybe we shouldn’t do that; maybe, NMB could be used; however, at this time, there was still concern regarding neuromuscular weakness as adverse effect

High-frequency oscillatory ventialation

• two negative trials sidelined this approach
• Ferguson et al. N Engl J Med 2013;368[9]:795 showed increase in mortality

Start of the modern discussion of NMB early to avoid asynchrony happened with the Forel et al. Crit Care Med 2006;34[11]:2749 which showed that less lung inflammation occurred with NMB

ACURASYS trial then showed that mod/sev ARDS could have mortality benefit with the use of NMB comparable to that seen in low tidal volume trial

• Papazian et al. N Engl J Med 2010;369:980

PETAL Network then looked into NMB via the ROSE trail

• this failed to confirm the mortality benefit that Papazian et al. saw in ACURASYS
• some will cite the heterogeneity of treatment effect as reason for not seeing mortality benefit
• others will say that there are important design differences between ACURASYS and ROSE
  • ROSE used the high PEEP algorithm to titrate PEEP to FiO2 rather than the conventional low PEEP approach (which was used in ARDSNet and ACURASYS trials)
  • theory: the high PEEP may have mitigated the NMB benefits
  • importantly, there was not a higher incidence of neuromuscular weakness in the NMB group
• despite the lack of clear mortality benefit in ROSE, NMB is still widely available, inexpensive, and easily performed per Co et al. Crit Care Med 2019

Question remains whether combining NMB and proning is the way to go

• Goligher et al. Am J Respir Crit Care Med 2014;190[1]:70 found that those pts who are recruitable with PEEP (those whose PaO2 increases w/ increasing PEEP in the face of unchanged or minimally-changing plateau pressure) may also demonstrate a mortality benefit
• though some clinicians are able to use proning without NMB, many are not able to use without NMB—in fact, NMB was widespread in PROSEVA