Effect of randomization to neuromuscular blockade on physical functional impairment and recovery in ARDS

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Project Summary/Abstract Background: The acute respiratory distress syndrome (ARDS) continues to be a major health problem, affecting nearly 200,000 people in the United States each year. Mortality is high (up to 40%), and nearly all survivors develop muscle loss and weakness during critical illness, termed ICU-acquired neuromuscular dysfunction. This neuromuscular dysfunction is associated with poor outcomes including: increased hospital mortality, delayed liberation from mechanical ventilation, prolonged hospitalization, impaired post-discharge functional activity, and continued risk of death among survivors of critical illness. Medications used during critical illness are frequently implicated in the cause of ICUAW, but data are inconclusive. For example, neuromuscular blocking agents (NMB) work directly on the neuromuscular junction and prevent muscle depolarization in response to nerve excitation. As a result, NMBAs can cause functional denervation and ultimately: neuropathy, myopathy, deconditioning, and prolonged neuromuscular weakness. However, NMB may also improve mortality in ARDS by reducing ventilator induced lung injury. Despite much debate about these risks and benefits, a randomized trial in ARDS patients is required to understand the effect of NMB on mortality, neuromuscular function, and recovery. The NHLBI PETAL Network will be conducting a randomized trial of NMB in ARDS, which provides a unique opportunity to study the effect of NMB on ICU-acquired neuromuscular dysfunction and recovery. Proposal and hypothesis: We propose to conduct an ancillary study at five of the PETAL network centers that will leverage the network infrastructure, complement the conduct of the clinical trial, and most importantly enhance the understanding of the utility of NMB for critically ill patients. We hypothesize that randomization to NMB will increase ICU-acquired neuromuscular dysfunction, leading to an increase in neuromyopathy early in critical illness, to impaired muscle strength and function at hospital discharge, and to reduced long term physical recovery. Specific Aims: Our specific aims are to determine the effect of randomization to NMB on development of neuromyopathy early in ARDS, on weakness at hospital discharge, and on physical functional recovery and healthcare utilization at 6 and 12 months after ARDS. We will conduct these aims by performing rigorous, standardized assessments of physical function using electrophysiology, ultrasound, hands-on strength and functional assessments, detailed questionnaires, and in-person follow-up after hospital discharge. We will use state-of-the art techniques for cohort retention and data analysis. With these results, we will definitively determine the acute and post-hospital effects of NMB on physical function. This knowledge is crucial for providing highest quality critical care that is focused not only on survival, but also the quality of survivorship.