Effect of Randomization to Neuromuscular Blockade on Physical Functional Impairment and Recovery in ARDS

Overview

The proposed work will determine the effect of neuromuscular blockade on physical function and recovery in patients with ARDS. The investigators will conduct a prospective ancillary study at five PETAL clinical centers that will evaluate the neuromuscular structure and function of ROSE (Reevaluation of Systemic Early Neuromuscular Blockade) patients during and after critical illness, including in-person assessments at 6 months after hospital discharge. The investigators hypothesize that patients randomized to NMB will have an increase in ICU-acquired neuromuscular dysfunction during and after critical illness.

The investigators will assess this dysfunction in different ways, appropriate for patients' stage of critical illness and anticipated recovery. During critical illness, the investigators will use nerve conduction studies (NCS) to assess nerve and muscle function, identifying presence of early neuromyopathy (primary outcome, Aim 1). Additional early assessments will include bedside ultrasound to determine muscle mass and echogenicity, indices of atrophy and loss of muscle architecture. Later in acute hospitalization as patients are able to participate in testing, the investigators will use hand grip dynamometry to assess muscle strength (primary outcome, Aim 2). Additional assessments at this time will be hand held dynamometry to determine proximal muscle strength, dual energy x-ray absorptiometry (DEXA) and repeat ultrasound to evaluate muscle mass, and short physical performance battery (SPPB) to assess activity. After hospital discharge-at 6 months after ARDS-the investigators will assess activity in-person using the SPPB (primary outcome, Aim 3). Additional post-hospital assessments include detailed evaluation of healthcare utilization, six minute walk testing (6MWT) to determine endurance, and repetition of previous assessments of muscle structure, function and strength to provide novel, detailed information of recovery process. Each aim tests a distinct hypothesis of the effect of randomization to NMB on ICU-acquired neuromuscular dysfunction, investigating different time points and aspects of physical function, so aims are not interdependent. For example, it is plausible that the direct toxicity of NMB on muscle will lead to early evidence of neuromyopathy, manifest as reduced muscle depolarization amplitudes with nerve stimulation. But if NMB attenuates lung injury, strength may be improved by hospital discharge, despite early injury to muscle.