Table 2.

Recommendations for Advancing the Study of Mechanisms Underlying Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome

Domain	Recommendation
Measurement and definition of brain and muscle dysfunction in ARDS	Establish diagnostic criteria for ARDS-related brain and muscle dysfunction for use in both clinical and research domains
	Explore patient outcome measures that incorporate patient-focused functional tasks (e.g., paying a bill or bathing independently)
	Evaluate how to incorporate evolving and adaptive patient preferences when determining primary outcomes of brain and muscle dysfunction
	Develop care pathways that explicitly screen for and proactively address unmet needs related to social determinants of health to improve physical and cognitive recovery (e.g., screening for food insecurity and connecting patients with local resources)
Pathogenesis of brain and muscle dysfunction	Investigate underlying pathological molecular pathways using traditional animal models of acute lung injury as well as more complex animal models that account for the heterogeneity of treatment and recovery environments
	Incorporate mechanisms known or suspected to be important in distinct but related syndromes of muscle and brain impairment (e.g., chemotherapy-related cognitive impairment or Alzheimer’s disease and related dementias)
	Explore approaches to manipulating the expression and/or biologic activity of proteins that promote muscle regeneration and repair during and after critical illness
Designing and testing interventions to improve brain and muscle dysfunction after ARDS	Use forward and reverse translational studies of brain and muscle dysfunction in ARDS to develop biologically plausible interventions to be tested in clinical trials
	Establish consensus on preferred statistical methods for analyzing the effect of interventions on functional outcomes of ARDS survivors in randomized trials
	Identify patients in ARDS trials who are resilient to expected brain and muscle dysfunction and develop models of resilience through reverse translational approaches
	Use hybrid implementation-effectiveness trial designs to study clinical effectiveness while generating implementation findings needed for spread and scaling
Other	Expand access to clinical and biologic data across studies and centers

For definition of abbreviations, see Table 1.