Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies

Abstract

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (V_T) 4-6 mL/kg of predicted body weight, plateau pressure (P_PLAT) < 30 cmH₂O, and driving pressure (∆P) < 14 cmH₂O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy.

Keywords: ARDS; acute respiratory distress syndrome; mechanical ventilation; pharmacologic therapies; phenotypes.

Figure 1

Ten golden rules to set the ventilator in patients with ARDS. V_T, tidal volume; PBW, predicted body weight; IBW, ideal body weight; Pplat, plateau pressure; ∆P, driving pressure; RR, respiratory rate; PEEP, positive end-expiratory pressure; MP, mechanical power; ECCO₂R, extracorporeal carbon dioxide removal; ECMO, extracorporeal membrane oxygenation; PaO₂, arterial partial pressure of oxygen; FiO₂, fraction of inspired oxygen; NMBAs, neuromuscular blocking agents; RMs, recruitment maneuvers.

Figure 2

Personalized medicine approach versus standard approach. ARDS, acute respiratory distress syndrome; PEEP, positive end-expiratory pressure. Applying personalized medicine using latent class analysis, two sub-phenotypes are identified, which positively respond to some pharmacotherapies and supportive treatments that previously failed to demonstrate benefits in a broader and inhomogeneous ARDS cohort.