Improved understanding of the respiratory drive pathophysiology could lead to earlier spontaneous breathing in severe acute respiratory distress syndrome.

UNLABELLED: Optimisation of the respiratory drive, as early as possible in the setting of severe acute respiratory distress syndrome (ARDS) and not its suppression, could be a new paradigm in the management of severe forms of ARDS. Severe ARDS is characterised by tachypnoea and hyperpnoea, a consequence of a high respiratory drive. Some patients require endotracheal intubation, controlled mechanical ventilation (CMV) and paralysis to prevent overt ventilatory failure and self-inflicted lung injury. Nevertheless, intubation, CMV and paralysis do not address per se the high respiratory drive, they only suppress it. Optimisation of the respiratory drive could be obtained by a multimodal approach that targets attenuation of fever, agitation, systemic and peripheral acidosis, inflammation, extravascular lung water and changes in carbon dioxide levels. The paradigm we present, based on pathophysiological considerations, is that as soon as these factors have been controlled, spontaneous breathing could resume because hypoxaemia is the least important input to the respiratory drive. Hypoxaemia could be handled by combining positive end-expiratory pressure (PEEP) to prevent early expiratory closure and low pressure support to minimise the work of breathing (WOB). 'Cooperative' sedation with alpha-2 agonists, supplemented with neuroleptics if required, is the pharmacological adjunct, administered immediately after intubation as the first-line sedation regimen during the multimodal approach. Given relative contraindications (hypovolaemia, auriculoventricular block, sick sinus syndrome), alpha-2 agonists can help attenuate or moderate fever, increased oxygen consumption VO2, agitation, high cardiac output, inflammation and acidosis. They may also help to preserve microcirculation, cognition and respiratory rhythm generation, thus promoting spontaneous breathing. Returning the physiology of respiratory, ventilatory, circulatory and autonomic systems to normal will support the paradigm of optimised respiratory drive favouring early spontaneous ventilation, at variance with deep sedation, extended paralysis, CMV and use of the prone position as therapeutic strategies in severe ARDS.

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