Should muscle relaxants be used in ARDS patients?
The recent ROSE trial (1) investigated the difference in 90-day mortality rates between mechanically ventilated ARDS patients who received an early and continuous infusion of neuromuscular blocking agent (NMBA) with concomitant deep sedation and those who received usual care with no routine NMBA and lighter sedation targets. All patients were suffering from moderate-to-severe ARDS and being treated with a strategy involving high PEEP. The background for the trial was uncertainty about the benefits of early continuous neuromuscular blockade in ARDS patients receiving mechanical ventilation. Results published in 2019 showed no difference in 90-day mortality between the two groups. These results are in direct conflict with results of the ACURASYS trial (2) published several years earlier, which showed a lower mortality rate in those patients who received muscle relaxants early on in their treatment.
In addition to showing no difference in mortality rates, results showed that the early use of a NMBA was associated with less physical activity, as well as a greater number of serious adverse cardiovascular events.
It is important to recognize the difference between the two trials. In the ROSE study, the investigators:
- Compared light sedation in the control group versus deep sedation and paralysis in the intervention group, while the ACURASYS trial compared deep sedation in the control group versus deep sedation and paralysis in the intervention group. The use of the lighter sedation strategy in the control group of the ROSE study may have decreased mortality in that group.
- Used higher PEEP than in the ACURASYS trial. This in itself could reduce the mortality rate in moderate-to-severe ARDS patients and thus negate the potential treatment effect of the early NMBA.
- Used the prone position much less frequently than in the ACURASYS trial. Prone positioning may reduce the risk of death in patients with ARDS and although it is not known whether use of early NMBA is more effective with prone positioning, it is a possible explanation for the difference in results from the two trials.
- Ended up with higher mortality rates overall, but found no difference between the control and the intervention groups.
Bearing these differences in mind, the question is not necessarily one of sedation strategy, but of ventilation strategy.
Prone positioning has been demonstrated as an effective treatment for ARDS (moderate-to-severe) patients. A recent study showed that prone positioning had an immediate beneficial effect on lung mechanics and a late lung recruitment effect independent of the PEEP strategy (3). However, as prone positioning requires deep sedation, this strategy should include the use of muscle relaxants.
The clinician therefore has two options:
- Keeping the patient in a supine position with light sedation and appropriate PEEP
- Using deep sedation, paralysis, and prone positioning
Which of these options is more lung protective is no doubt dependent on various factors, including the severity of ARDS, the size of the aerated lung, recruitability, etc. This question is currently the subject of further research.
- National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Moss M, Huang DT, et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019;380(21):1997–2008. doi:10.1056/NEJMoa1901686
- Papazian L, et al. Neuromuscular blockers in early acute respiratory distress syndrome. The New England Journal of Medicine. 2010. 363(12):1107-1116
- Mezidi M, Parrilla FJ, Yonis H, et al. Effects of positive end-expiratory pressure strategy in supine and prone position on lung and chest wall mechanics in acute respiratory distress syndrome. Ann Intensive Care. 2018;8(1):86. Published 2018 Sep 10. doi:10.1186/s13613-018-0434-2
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