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Objectives: Recovery from ICU-acquired muscle weakness extends beyond hospital stay. We hypothesized that immobilization, more than inflammation, plays a prominent role in the delayed recovery from critical illness.Design: Prospective, randomized, controlled, experimental study.Setting: Animal laboratory, university hospital.Subjects: Male Sprague-Dawley rats.Interventions: Animals were divided to have one hind limb immobilized (n = 129) or sham-immobilized (n = 129) on day -12. After surgery, rats were further assigned to two subgroups. To induce inflammation, rats received three IV injections of Corynebacterium parvum on days -12, -8, and -4. Controls received saline at the respective time-points. At day 0, the limbs were remobilized and recovery from inflammation and/or immobilization was followed for 36 days.Measurements and Main Results: At day 0 and after 4, 12, or 36 days of recovery, maximum tetanic tension and tetanic fade (functional parameters = primary outcome variables) as well as nicotinic acetylcholine receptor expression, muscle mass, and histologic changes (structural parameters = secondary outcome variables) were measured. Impaired maximum tetanic tension, decreased tibialis muscle mass, and fiber diameter due to inflammation alone recovered by day 4. Tetanic fade was not affected by inflammation. Immobilization-induced loss of tibialis muscle mass, decreased fiber diameter, and tetanic fade did not return to normal until day 36, while maximum tetanic tension had recovered at that time. In the presence of inflammation and immobilization, the decrease in tibialis muscle mass, fiber diameter, and maximum tetanic tension, as well as decreased tetanic fade persisted until day 36. Up-regulation of nicotinic acetylcholine receptors normalized before day 4 following inflammation, but persisted until day 4 following immobilization.Conclusions: In our model, muscle function and structure recovered from inflammation within 4-12 days. Immobilization-induced neuromuscular changes, however, persisted even at day 36, especially if inflammation was concomitant. [ABSTRACT FROM AUTHOR]

Purpose of Review: The present review provides a summary of the literature on recent development of new neuromuscular blocking agents and presents clinically well established and new reversal agents., Recent Findings: Anesthesiologists are still waiting for the ideal neuromuscular blocking agent with a succinylcholine-like rapid onset and offset without side effects. Recent drug development led to a new series of neuromuscular compounds, called the chlorofumarates such as gantacurium, CW002, and CW011. These drugs have a promising pharmacodynamic profile; importantly, they can rapidly be reversed by L-cysteine adduction without relevant side effects. In addition, a new spectrum of reversal agents are currently examined in preclinical studies: adamgammadex sodium, a modified γ-cyclodextrin derivate that forms an inactive tight inclusion complex with rocuronium or vecuronium and calabadions, capable of reversing both benzylisoquinolines and steroidal neuromuscular blocking agents., Summary: Although the recent advancements in neuromuscular research are very promising, to date, the presented drugs are currently not available for clinical use. Clinical studies will determine the role of these developments in anesthesia practice. Therefore, well established combinations such as rocuronium-sugammadex are popular in clinical practice to offer quick paralysis for intubation and to optimize surgical conditions, while providing a fast neuromuscular recovery at the end of surgery.