Thread by @WellingtonICU

This week's @WellingtonICU #Twitterjournalclub was prepared by @oweepower and is on the #ROSEtrial
nejm.org/doi/full/10.10…

Multicenter, unblinded, randomized trial of patients with moderate to
severe ARDS

Their aim was to determine the efficacy and safety of early neuromuscular blockade (NMB) with heavy sedation c.f. use of lighter sedation targets without NMB

There are potential benefits with use of early NMB = reduced patient-ventilator dyssynchrony, reduced WOB, reduced accumulation of alveolar fluid.

But also potential major pitfalls of admin of NMB = subsequent neuromuscular weakness, SEs associated with requirement for deep sedation during NMB.

Despite ACURASYS trial suggesting lower mortality with early NMB in ARDS, it is not widely adopted – only weakly recommended in current guidelines.

In order to maintain some consistency with ACURASYS trial – they used the same neuromuscular blocker (cisatracurium), same dosing regimen and duration of treatment

Key difference from ACURASYS was the use of lighter sedation targets in control group – more consistent with current practice.

To keep other aspects consistent with current practice, they also specified mechanical ventilation (MV) protocol, and recommended use of conservative fluid strategy

Their primary end-point was in-hospital death from any cause at 90 days. There were a number of secondary end points, end points assessed at 3, 6, and 12 months as well as safety end points

Between Jan 2016 – April 2018, they screened 4848 patients at 48 hospitals across US. 1006 patients included in primary analysis. 501 were assigned to intervention, 505 to control groups – baseline characteristics were similar.

For the intervention group, 488 (of 501) received cisatracurium infusion. Overall this group received deeper sedation up to day 3, had lower PEEP in day 1, lower minute ventilation, and lower FiO2.

Despite the above differences between the two groups, there were no differences in primary end points of survival at day 90. Also no differences were found in most of secondary end points.

The only difference was found in cardiovascular SOFA score which was higher in the intervention group but only for day 1 and 2 (possibly related to deeper
sedation during this period)

Patient-reported outcomes were similar at 3, 6, and 12months in all aspects assessed. No difference were found for ICU-acquired weakness.

Strengths
Well designed and well conducted with high adherence to NMB protocol, and high adherence to recommended ventilation and fluid strategies.

Limitations
1. Most common reason for exclusion was previous receipt of NMB – clinicians
possibly were identifying patients more likely to benefit from NMB use

2. Lack of blinding– source of potential bias

3. Despite stating ‘no stopping rule for futility’ – they stopped for futility

4. Study conducted in centres in US only – population differences c.f. Australasia. Also use of cisatracurium – not widely available in NZ.

Conclusion:
In patients with mod-to-severe ARDS, administration of early continuous infusion
of cisatracurium did not result in lower mortality at 90 days c.f. usual care
with lighter sedation

Thoughts:
If there is an issue with ventilation in mod-to-severe ARDS e.g. due to ventilator
dyssynchrony – it’s probably ok to use NMB infusion in the short term. Equally,
if NMB use can be avoided, then it’s probably best to do so.

This study confirms that what we are currently doing is probably best for the patient. Use lighter sedation strategy, and reserve the use of paralysis for when the need for it arises. Reassuring and logical.

@threadreaderapp unroll please