Pathophysiological Hypothesis of the Beneficial Effects of NMBAs

The results of the three available RCTs about the use of NMBAs during the early phase of ARDS indicate that the effect of the treatment on oxygenation becomes significant after 24 h. Moreover, in the ACURASYS trial, the Kaplan-Meier survival curves did not separate until 18 days of treatment. These observations together with the available knowledge regarding the use of NMBAs for shorter periods in patients with healthy lungs raise hypotheses regarding the manners in which NMBAs could be beneficial (Fig. 12.2) during the acute phase of severe ARDS. Several mechanisms may be involved and are most likely interrelated. Slutsky [25] proposed a summary of the effects of NMBAs that included the following main points:

  • • Patient-to-ventilator dyssynchronies are reduced, and the control of tidal volume is improved, which leads to decreases in baro- and volutrauma as well as a decrease in atelectrauma due to the inhibition of active expiration and the improved control of the PEEP. This latter effect is associated with decreases in lung blood flow and alveolar-capillary permeability.
  • • NMBA use is associated with a decrease in respiratory drive that is classically associated with hypoxaemia and permissive hypercapnia.
  • • NMBA use leads to a decrease in biotrauma, an inhibition of the translocation of inflammatory mediators from the alveolar space to the circulation and a decrease in associated organ failure. These suppositions are supported by the decreased production of pro-inflammatory cytokines in both the lung and blood observed by Forel et al. [15]. Moreover, a direct anti-inflammatory role of cisatracurium via nicotinic acetylcholine receptor-a 1 has recently been demonstrated in in vitro and murine models [26].
  • • NMBA use results in a progressive increase in the functional residual capacity and a decrease in intrapulmonary shunting. The improvement in the ventilation- perfusion ratio may also be related to the more uniform distribution of the pulmonary perfusion due to the application of lower pulmonary pressure, which favours the perfusion of ventilated areas and decreases intrapulmonary shunting.
  • • NMBA use results in decreases in muscle oxygen consumption and cardiac output [27]; however, similar findings have not been reported by other authors [28] and may depend on ARDS severity, sedation deepness and work of breathing before paralysis [29].
 
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