NMB in Early ARDS.

A fascinating study from the NEJM.

Neuromuscular Blockers in Early ARDS. Papazian, L et al. NEJM. Vol 6, 12, 2010.

This RCT gave a 48 hr infusion of cis-atricurium to early (<24hrs) ARDS patients. It is the first study to show a mortality difference in this condition since ARDSnet a decade ago (although caution is required as it was underpowered). Whilst it is likely that a large proportion of the population included in this study (early, severe ARDS) will already be on NMB to aid ventilation, there has up until now been an assumption that this therapy was a necessary harm (due to the risk of critical illness polyneuropathy and subsequent slow weaning). This study questions that wisdom, showing both a reduction in adjusted mortality at 90 days (although not at 28) and no increase in the risk of CIPN. The results need to be taken with caution, but are certainly interesting and if confirmed may offer an important advance. There is further detailed analysis of the paper in the presentation ‘Atricurium ARDS’ in the blue box. Remember that restrictions on comments have been lifted on Critical Insight, no sign in required – so let us know your opinions.

6 comments so far

  1. precordialthump on

    This is a provacative paper that’s for sure. The mortality benefit probably reflects decreased barotrauma in the paralysed group — the rates of pneumothorax in the 2 arms was 11% for control and 4% for neuromuscular bloackade.

    However there are alot of questions to answer:
    – could increased analgesia/ sedation have reduced the rates of pneumothorax in the control group?
    – how plausible is it that 2 days of paralysis would result in such marked survival benefits? What is the mechanism?
    – although 90d survival was measured, muscle weakness was only assessed up to 28d – are there delayed cases of critical illness polynuropathy being missed?
    – How was the adequacy of blockade assured in the absence of train-of-four testing?
    – could the benefit be a property of cis- atracurium rather than neuromuscular blockade?
    – is the blinding of this study suspect? If the NMB group is fully paralysed only the control group would trigger ventilations, thus breaking randomisation.
    – How was ventilator dyssynchrony dealt with? This is not described in the paper – could this be killing patients?
    – Was volume-control ventilation appropriate? The patients in this study were sick – PaO2:FiO2 of 100, compared with about 150 in the ARDSNet study where they got their ventilation protocol from. Patients were excluded if they had refractory hypoxemia in the ARDSnet study. The low-volume ventilation protocol may not suitable for these severely-effective patients. Although, similar rates of barotrauma were seen in the ARDSnet study.
    – how does this apply to other ventilation modes like APRV that tend to be used in severe ARDS these days?

    Chris Nickson

  2. danharvey on

    Thanks for great comments Chris. I aggree the paper poses more questions than answers. It’s interesting that despite pneumothorax rates being different, plateaux pressures were equal in both groups. Are we using the wrong parameter when assessing the applied pressure?

    Has this paper changed your practise? It has changed mine, starting paralysis now means an infusion (ideally 48hours) rather than bolts dose.

  3. precordialthump on

    Hi Dan,
    Interesting point on the plateau pressure – will be interesting to see if it’s borne out in other studies. Don’t have a great answer!
    Don’t think this changes practice – in severe ARDS I wouldn’t be using volume-controlled ventilation – more likely to use APRV. Was using NMBs anyway if absolutely required – though not so much as an infusion, though its clearly an option if needed (not routine).
    It seems to offer some reassurance that it is OK to use NMBs if needed, given the unchanged rates of polyneuropathy at 28d.

  4. danharvey on

    We commonly leave on pressure control, but inverse I:E ratios (which is therefore essentially APRV) or oscillate, so take you point that the trial may not be applicable.

    The reason for moving to an infusion over a bolus is that the control arm in the trial were allowed open label bolus atricurium (which mirrors my previous practise) and did worse. We’ve stopped short of making a 48hour infusion routine, although we are considering it on the basis of this trial.

    I wonder if ANZICS will do us the usual service of running a properly powered RCT and disproving the initial positive european study!

  5. John Lambert on

    This is a wonderful demonstration of the harm of volume controlled ventilation, and how paralysing patients allows you to use this mode fractionally more safely – the mortality and pneumothorax rates are horrifying and unacceptable, especially considering that the average P/F ratios and FiO2 and PO2 averages demonstrate generous (over) oxygenation, underPEEPing and really not very sick lungs, despite the high mortality rate!

    The fascinating piece of information is the HEAVIER use of sedatives, and in particular Ketamine in the NMBA group!

    Morale of this study – don’t use volume controlled ventilation strategies (note no mention of use of PRVC/VC+/Autoflow, which would be a lot better)

  6. […] can register and submit their own posts. The blog most recently featured the provocative topic of NMB in Early ARDS. Free Emergency Medicine TalksA great talk by Mervyn Singer called “Less is More in […]

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