Effects of s-ketamine and midazolam on respiratory variability: A randomized controlled pilot trial

1. Midazolam significantly reduces respiratory variability, leading to a more uniform and less adaptable breathing pattern, which may increase risk in patients with compromised respiratory function.

2. S-ketamine largely preserves respiratory variability, suggesting it may be a safer sedative option for patients who require maintenance of spontaneous breathing.

Evidence Rating Level: 1 (Excellent) 

This randomized controlled pilot trial investigated the effects of s-ketamine and midazolam on respiratory variability, an indicator of adaptability of the respiratory system, in women with fibromyalgia. Twenty-eight participants were randomized to receive intravenous infusions of s-ketamine, midazolam, or saline in a blinded, crossover design across three visits. Respiratory parameters, including mean respiratory rate, variability of respiratory rate, and variability of tidal volume, were continuously measured non-invasively using a bio-impedance method. Data from 57 experimental sessions were analyzed with linear mixed models. Midazolam significantly reduced both respiratory rate variability by 37% and tidal volume variability by 51%, without affecting mean respiratory rate. S-ketamine produced a smaller reduction in tidal volume variability (27%) but did not affect respiratory rate variability. Post hoc analysis confirmed significant differences between the two drugs across all parameters. The findings suggest that midazolam induces a more regular and less adaptable breathing pattern, whereas s-ketamine largely preserves respiratory variability. These results have clinical implications in anesthesiology and critical care, as preserved variability may be advantageous for patients requiring sedation while maintaining spontaneous breathing. Further studies in larger and more diverse patient populations are needed to determine the clinical significance of these differential effects.

Click to read this study in PLOS One

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