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Neuromuscular blockade (NMB) is a commonly used strategy in critical care, including management of refractory intracranial pressure, intra-abdominal hypertension, or shivering during therapeutic hypothermia after cardiac arrest and as a rescue strategy in patients with the acute respiratory distress syndrome (ARDS). The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) observational dataset demonstrated NMB use in 21.7% of all 2,377 ARDS patients and in 37.8% of Berlin severe ARDS patients (1). In a Canadian clinical trial, nearly two third of patients (442/664) enrolled had severe ARDS with refractory hypoxemia, defined as a PaO 2 of less than 60 mm Hg on an FIO 2 of 100%. Forty-two percent of these patients underwent NMB during mechanical ventilation (2). Additionally, prone positioning, a rescue maneuver with a strong recommendation for use in patients with severe ARDS, frequently requires the concomitant use of NMB (3). Although the recently published Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial failed to confirm the benefits of NMB early (< 48 hr) in the course of ARDS (4), NMB may still be employed in refractory hypoxemia to improve oxygenation, facilitate prone ventilation, and to potentially limit ventilator-associated lung injury, ostensibly through the prevention of regional tidal hyperinflation due to pendelluft, reverse triggering, or dynamic hyperinflation (5, 6). Optimal use of NMB in critically ill patients has remained controversial (7, 8). NMB use has been associated with an increased prevalence of neuromuscular weakness following recovery from sepsis, ARDS, and respiratory failure. This phenomenon called “critical illness polyneuromyopathy or ICU-acquired weakness (ICUAW)” is related to the duration of mechanical ventilation and is believed to occur as a result of disuse atrophy that leads to prolonged weakness persisting after discharge from the ICU (9). To the extent patients with ARDS often have a prolonged course of mechanical ventilation during which time NMB may be employed for multiple days as a rescue maneuver, the risk of developing ICUAW is especially of concern in this group of patients. Studies involving NMB for patients with asthma receiving invasive mechanical ventilation had also inferred an association between NMB use and neuromuscular weakness as well as the duration of mechanical ventilation (10). Here, the absence of sepsis as a potential confounder strengthened the notion of this association. However, these studies involved the use of aminosteroid neuromuscular-blocking agents such as pancuronium, vecuronium, and rocuronium. The aminosteroid group relies predominantly on a combination of hepatic and renal elimination, potentially generating a prolonged halflife of NMB resulting in the potential for extended paralysis even after cessation of medication. Attempts to minimize aminosteroid NMB drug delivery, using train-of-four peripheral nerve stimulators to guide the depth of paralysis, had been able to demonstrate a shorter time to recovery of spontaneous ventilation after NMB discontinuation (11). Despite the risk of prolonged drug effect in patients with organ dysfunction, it was never demonstrated that limiting drug administration via the use of train-of-four stimulators would mitigate the development of ICUAW (10). Although prevalent decades ago (12), the use of aminosteroid neuromuscular-blocking agents in patients with respiratory failure has largely been supplanted by the use of benzylisoquinolinium NMB agents (atracurium and cisatracurium). The half-life of these agents is about 30 minutes and is unaffected by renal or hepatic organ dysfunction. Broken down in the blood, these agents’ unique pharmacokinetics by Hoffman elimination results in no prolongation of drug effect. To wit, in a large, observational cohort, patients with Both authors: Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI. Supported, in part, by grant U01 HL-123031 from the National Heart, Lung and Blood Institute (to Dr. Hyzy). Dr. Hyzy’s institution received funding from National Heart, Lung and Blood Institute, and he received support for article research from the National Institutes of Health. Dr. Co has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected] Rescue Neuromuscular Blockade in Acute Respiratory Distress Syndrome Should Be Flat Dose