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Perspectives: The Appropriate Place of NMBAs in ARDS Treatment

Clear recent recommendations concerning the use of NMBAs for ARDS are lacking. The most recent guidelines from 2002 [1] reduce the role of NMBAs to “facilitating mechanical ventilation when sedation alone is inadequate”. These guidelines were created before the RCTs were conducted and appear to be obsolete. The recent data on the beneficial effects of NMBAs on mortality have modified their use. In a recent large international survey conducted in 50 countries, NMBAs were found to be the most frequently used adjunctive measure in severe ARDS [7]. NMBAs were also extensively used in the PROSEVA study, which demonstrated the beneficial effect of prone positioning on mortality [6]. Overall, that NMBAs have a crucial role in the management of ARDS seems to no longer be questionable. However, the available literature conveys the following “rules” with respect to the use of NMBAs:

  • • First, NMBAs should be used to paralyse patients in the early phase of the evolution of ARDS.
  • • Second, short courses of treatment should be administered to limit the occurrence of ICUAW. Forty-eight-hour treatments were used in the ACURASYS study [16], but shorter treatments (24 h) might be sufficient if the evolution is rapid and favourable. In contrast, in the most severe cases, a longer period may be required (72-96 h), particularly for patients who require several days of PP (as in the PROSEVA study) and those who require extracorporeal life support.
  • • Third, NMBAs should be reserved for the most hypoxaemic patients (including severe ARDS and the most hypoxaemic cases of moderate ARDS). A PaO2/FiO2 ratio cut-off of 120 can be proposed based on the ACURASYS study data [16], but a ratio of 150 might also be used. This cut-off is proposed in the most recent guidelines of the Surviving Sepsis Campaign, which support the use of short- course treatment with NMBAs during sepsis-related ARDS [49]. Moreover, NMBAs are almost always associated with PP [6], and PP has been demonstrated to be beneficial for patients with a PaO2/FiO2 ratio below 150. The Reevaluation Of Systemic Early Neuromuscular Blockade (ROSE study NCT02509078) study is currently recruiting patients with PaO2/FiO2 ratios below 150 and will hopefully help to form a conclusion.
  • • Fourth, NMBAs should be integrated into ventilatory strategies that allow for spontaneous ventilation as soon as the ventilatory parameters improve (Fig. 12.3). Indeed, in the ACURASYS study, following the initial 48-h period, NMBAs were discontinued, sedatives were reduced and pressure support ventilation was introduced in all patients with FiO2 values less than or equal to 0.6. This concept was also present in the PROSEVA study; in this trial, when the PaO2/FiO2 ratio was >150 mmHg, the PEEP was <10 cmH2O and the FiO2 was <60%, the PP sessions, sedation and paralysis were stopped to allow for spontaneous efforts.

Adhering to these conditions might ensure the acquisition of the beneficial effects of NMBAs while preventing their deleterious side effects.

However, several questions remain to be answered. The potential antiinflammatory properties of cisatracurium [15, 26] and the efficacies of other molecules need to be investigated, the appropriate dose needs to be identified (in the ACURASYS study, high and constant doses were used to preserve the blinding for both groups), NMBA efficacy needs to be examined with train-of-four monitors and the appropriate target paralysis depth needs to be clarified.

The place of NMBAs in protective ventilation in ARDS. NMBAs neuromuscular blocking agents, ARDS acute respiratory distress syndrome

Fig. 12.3 The place of NMBAs in protective ventilation in ARDS. NMBAs neuromuscular blocking agents, ARDS acute respiratory distress syndrome

Conclusion

NMBAs are the most frequently used pharmacological treatment for ARDS. Recent strong evidence indicates that NMBAs improve survival in the most severe patients. Moreover, early and short-term administration is not associated with neuromuscular side effects and should be followed with a ventilator strategy that allows for spontaneous breathing as soon as gas exchange improves. Further studies will help to precisely identify the appropriate place of NMBAs in the treatment of moderate ARDS, the doses that should be used and the monitoring that must be performed.

 
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