Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, and sevoflurane on sleep homeostasis in rats

• Published in: British journal of anaesthesia : BJA Vol. 132; no. 6; pp. 1248 - 1259
• Main Authors: Silverstein, Brian H., Parkar, Anjum, Groenhout, Trent, Fracz, Zuzanna, Fryzel, Anna M., Fields, Christopher W., Nelson, Amanda, Liu, Tiecheng, Vanini, Giancarlo, Mashour, George A., Pal, Dinesh
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2024; Elsevier
• Subjects: Critical Care; dexmedetomidine; functional connectivity; phase-amplitude coupling; propofol; rat; sedation; sevoflurane; sleep homeostasis; dexmedetomidine; functional connectivity; rat; propofol; sleep homeostasis; sevoflurane; phase-amplitude coupling; sedation
• ISSN: 0007-0912; 1471-6771; 1471-6771
• DOI: 10.1016/j.bja.2023.11.014

Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01). In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.